Sodium balance and jejunal ion and water absorption in Dahl salt-sensitive and salt-resistant rats

1. Apparent Na+ absorption and jejunal water, Na+, Cl- and K+ absorption in vivo was evaluated in young (prepubertal) and adult Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats kept on a low-salt (low-salt rat chow + distilled water) or a high-salt diet (HS1 diet: NaCl-enriched rat chow + distilled water; HS2 diet: standard rat chow + 1% saline as drinking fluid). These two high-salt diets were chosen because the HS1 regimen has been shown to increase blood pressure (BP) in DS rats and the HS2 regimen decreases jejunal water and ion absorption in normotensive Wistar rats. 2. The HS1 or HS2 diet increased BP in young and adult DS rats but had no effect on the BP of young and adult DR rats. 3. Irrespective of dietary Na+ intake, no significant difference of apparent Na+ absorption (dietary Na+ intake minus faecal Na+ output) was observed between DS and DR rats both in prepuberty and in adulthood. Young DS rats kept on a low-salt diet had increased faecal Na+ output in comparison with young DR rats. This difference disappeared with increasing dietary Na+ intake. 4. There were no interstrain differences on the effect of a high-salt diet on jejunal Na+ and K+ absorption in young and adult DS and DR rats. However, high-salt diets stimulated jejunal water and Cl- absorption in young DS rats, but not in adult DS rats and young and adult DR rats. Interstrain differences of water and Cl- absorption were observed only in adulthood. Adult DR rats kept on an HS2 diet absorbed more water and Cl- than their DS counterparts. 5. Our results do not indicate any abnormalities of apparent Na+ absorption and jejunal water and electrolyte transport in DS and DR rats. We conclude that there is no relationship between intestinal Na+ absorption and sensitivity or resistance to induction of experimental salt hypertension.     

The role of blood pressure and aldosterone in the production of hemorrhagic stroke in captopril-treated hypertensive rats

BACKGROUND AND PURPOSE: We tested the hypothesis that the lowering of plasma aldosterone levels contributed to the antistroke effects of captopril treatment in Wistar Kyoto stroke-prone spontaneously hypertensive rats (SHRSP). METHODS: The suppression of plasma aldosterone by captopril treatment (50 mg.kg-1.d-1) was prevented by the subcutaneous infusion of aldosterone into captopril-treated SHRSP. We studied the effect this had on blood pressure (BP) and stroke development. RESULTS: SHRSP fed a Japanese-style diet containing 4% NaCl developed hypertension and a 100% mortality associated with intracerebral hemorrhage by 14 weeks of age. Captopril treatment from 6 weeks of age did not lower the BP but increased survival past 35 weeks of age. Hydralazine treatment (40 to 80 mg/L of drinking water) lowered BP in SHRSP but was less effective than captopril in retarding stroke. Plasma aldosterone levels were elevated with age in SHRSP after 10 weeks and were higher in poststroke versus prestroke SHRSP. Captopril treatment suppressed plasma aldosterone. When we elevated plasma aldosterone in captopril-treated SHRSP to levels between those present in untreated pre- and poststroke SHRSP, the ability of captopril to retard stroke development was negated. The effects of aldosterone were mimicked by deoxycorticosterone (40 mg/kg, SC2 times/wk) but not by dexamethasone (0.1 mg.kg-1.d-1, SC). Spironolactone treatment (20 mg.kg-1.d-1, SC) of SHRSP reduced BP but had little effect on stroke development. CONCLUSION: Elevations in plasma aldosterone enhance stroke development within captopril-treated SHRSP through mechanisms that do not involve stimulation of mineralocorticoid receptors or the enhancement of hypertension. The antistroke effects of captopril treatment may be partially mediated through the suppression of plasma aldosterone.     

Relationship between nifedipine sensitivity of aortae and blood pressure of stroke-prone spontaneously hypertensive rats

1. We have previously described an increased sensitivity to inhibition by nifedipine of noradrenaline-induced contractures of blood vessels in hypertension. In this study we have investigated whether changes in blood pressure (BP) change the sensitivity to nifedipine and K+ of aortic rings from normotensive (Wistar-Kyoto rats, WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). 2. SHRSP were treated with: hydralazine plus hydrochlorothiazide; captopril plus hydrochlorothiazide; hydralazine plus guanethidine; or captopril alone. WKY rats were treated with deoxycorticosterone acetate (DOCA) and NaCl. Treatment commenced from 5 weeks of age and continued until 13-15 weeks. 3. The SHRSP treatments produced similar reductions in BP, and the BP of all the treated groups were significantly lower than the mean BP of untreated SHRSP (201.0 +/- 7.7 mmHg). The mean BP of the treated WKY rats (134.2 +/- 7.6 mmHg) was significantly higher than the mean BP of the untreated WKY rats (86.8 +/- 7.4 mmHg). 4. An area-under-curve (AUC) analysis of the inhibitory effects of nifedipine on responses of aortae to noradrenaline showed no differences between treated and untreated SHRSP groups (overall mean 40.6 +/- 1.9% and 43.4 +/- 3.4% inhibition of control AUC, respectively), or between DOCA-salt treated WKY and untreated WKY groups (58.8 +/- 5.9 and 64.8 +/- 2.3, respectively). Noradrenaline-induced contractures of aortae from all SHRSP groups were significantly more sensitive to inhibition by nifedipine than aortae from both WKY groups. 5. The molar concentration of agonist required to evoke 50% of the maximum response (EC50) values for potassium chloride (KCl) were significantly increased in the aortae of all treated SHRSP groups in comparison to those from untreated SHRSP (treated SHRSP groups, 15.53 +/- 0.68 mmol/L vs untreated SHRSP group, 11.36 +/- 1.10 mmol/L). The EC50 values for KCl for the aortae from the DOCA-treated WKY rats were significantly less than those from aortae of the untreated WKY (11.80 +/- 0.80 and 17.08 +/- 1.50 mmol/L, respectively). 6. We conclude that reduction (in SHRSP) or increase (in WKY) of the BP has no effect on the sensitivity of aortic smooth muscle to the inhibitory effects of nifedipine on responses to noradrenaline, suggesting that alterations in voltage-dependent Ca2+ mechanisms may be a primary phenomenon in the SHRSP. In contrast, the fact that sensitivity to KCl changes in the treated SHRSP and WKY aortae suggests such sensitivity is secondary to the BP and thus a separate phenomenon from voltage-dependent Ca2+ mechanisms.     

Time course of lithium-induced alterations in renal and endocrine function in normal and Brattleboro rats with hypothalamic diabetes insipidus

1. A lithium chloride (1.1 g/kg) supplemented diet was given to Long Evans (LE) and Brattleboro (DI) rats to investigate its actions in the presence (LE) and absence (DI) of vasopressin. 2. During the first 24 h, Li-supplemented LE rats displayed an initial water deficit (drinking less than renal output), increased plasma antidiuretic (ADH) titres and slightly increased plasma renin activities (PRA) and plasma osmolarities. Such changes were qualitatively similar to those seen in rats fed a normal diet, but deprived of water for 24 hours. After 12 days, the Li-supplemented rats had elevated plasma ADH titres, but reduced pituitary oxytocic and antidiuretic activities. 3. The urinary losses of Na, K and Cl exceeded dietary intakes in LE rats on the introduction of the Li-supplement, and the urinary osmolarity fell by 50%. Electrolyte balances were gradually re-established, although drinking and urine production increased in parallel to reach twice the control values by day 12 of the supplement. 4. Aldosterone and corticosterone secretory rates and their peripheral plasma concentrations were unchanged both after 24 h and 28 days of the Li-supplement. 5. Li elicited no water deficit or saluresis in DI rats, and although the polyuria and polydipsia were exacerbated, urinary osmolarity did not change over the 12 day observation period. 6. Li increased Ca excretion in both rat types; after 12 days the PRA of DI but not LE animals were increased. 7. It is concluded that the overall renal actions of Li are tempered by vasopressin rather than adrenocorticosteroids.     

Failure of NaHCO3 and KHCO3 to inhibit renin in the rat

To evaluate the contribution of chloride to NaCl- and KCl-induced renin inhibition, renin responses to NaCl or NaHCO3 and to KCl or KHCO3 loading were compared in NaCl-deprived rats. Sodium balance in animals drinking isotonic NaHCO3 and NaCl for 9 days did not differ (P greater than 0.40); K+ balance was less positive in NaHCO3-drinking animals (P less than 0.005). Plasma renin activity (PRA) in NaCl-loaded (16.5 ng/ml per h +/- 4.4 SE), but not in NaHCO3-loaded rats (57.2 +/- 9.8), was lower (P less than 0.005) than in NaCl-deprived controls (44.8 +/- 4.7). Renal renin content (RRC) of NaCl but not of NaHCO3-drinking animals was also decreased (P less than 0.02). Both PRA and RRC of KCl- but not of KHCO3-loaded rats (5 meq K+/10 g diet) were lower (P less than 0.01) than in NaCl-deprived controls. After acute intravenous expansion with isotonic NaCl or NaHCO3, increases of plasma volume and plasma K+ did not differ (P greater than 0.05). However, PRA of NaCl-expanded rats (11.8 +/- 3.8) was lower (P less than 0.05) than in NaHCO3-expanded animals (29.7 +/- 8.5). The failure of NaHCO3 and KHCO3 to inhibit renin suggests a role for chloride in mediating the renin responses to Na+ and K+.     

The importance of studying the renin-angiotensin-aldosterone system in essential arterial hypertension in clinical practice. Activity of the renin-angiotensin-aldosterone system during treatment of hypertension with ACE-inhibitors and beta blockers

The authors assessed in 20 subjects with mild or medium severe arterial hypertension basal and stimulated values of plasma renin activity (PRA) and aldosterone before onset of treatment and after 6-week therapy with enalapril (ENAP KRKA) or metoprolol (Vasocardin Slovakofarma). PRA and aldosterone secretion was stimulated by a vertical position and by administration of 40 mg furosemide by the i.v. This test proved suitable for assessment of secondary arterial hypertension in different forms of primary hyperaldosteronism and for expressing suspicion of renovascular hypertension and hypertension with affection of the renal arteries resp. Based on PRA levels, arterial hypertension can be divided into normorenin, high-renin and low-renin hypertension. This classification is, however, of no value for selection of treatment and the prognosis of hypertension. Each level of PRA can be associated with three different aldosterone levels. PRA and aldosterone did not correlate with urinary K, Na excretion nor with blood pressure. During treatment with ACE inhibitor PRA rose while basal as well as stimulated aldosterone levels declined. After administration of betablockers basal as well as stimulated PRA and aldosterone levels declined.     

Agonist and antagonist effects of Sar1-ala8--angiotensin II in salt-loaded and salt-depleted normal man

1 Three normal subjects were infused with Sar1-ala8-angiotensin II (Saralasin, P113) whilst on a high sodium (200 mEq + normal diet) and a low sodium (10 mEq diet) intake. 2 On the high sodium intake when angiotensin II and plasma renin activity (PRA) were suppressed, P113 infusion (5-10 mug kg-1 min-1) caused a slight rise in BP and a marked drop in urine flow and sodium excretion, with a fall in glomerular filtration rate, and effective renal plasma flow. 3 On the low sodium intake, when angiotensin II and PRA were increased, P113 infusion (5-10 mugkg-1 min-1) caused no change in blood pressure, urine flow or sodium excretion. However, when P113 was infused at an incremental rate starting at 0.25 mug kg-1 min-1 there was a fall in standing BP, which was maximal at an infusion rate of 1 mug kg-1 min-1, and this fall in standing BP was largely abolished as the rate of infusion was increased to 10 mug kg-1 min -1. 4 These results show firstly that angiotension II is involved in maintaning standing blood pressure during dietary sodium depletion in normal man and secondly that P113 does have agonist as well as antagonist activity in normal man, the effect depending on the level of angiotension II and sodium intake. When looking for angiotensin II mediated hypertension it may ne important to use an incremental rate of infusion of P113 as the agonist activity of larger doses may mask its hypotensive action.     

Dietary docosahexaenoic acid increases cerebral acetylcholine levels and improves passive avoidance performance in stroke-prone spontaneously hypertensive rats

We have recently shown that inferior performance in passive avoidance task is accompanied with decreased hippocampal choline (Ch) in stroke-prone spontaneously hypertensive rats (SHRSP) compared with normotensive control Wistar-Kyoto rats (WKY). We also reported that dietary docosahexaenoic acid (DHA) suppresses the development of hypertension and stroke-related behavioral changes, resulting in the prolongation of the life span of SHRSP. In this study, we examined the effect of dietary DHA on the cerebral acetylcholine (ACh) levels and learning performance in passive avoidance tasks in SHRSP. The arachidonic acid decreased and the DHA increased in plasma lipids dose dependently with dietary DHA treatments, which decreased the systolic blood pressure in SHRSP. Dietary DHA significantly restored the significantly inferior learning performance in passive avoidance response observed in control SHRSP (DHA 0%). Furthermore, the hippocampal ACh levels were correlated positively with the total response latency in passive avoidance tasks. These results suggest that cholinergic dysfunction in the brain of control SHRSP is responsible, at least in part, for the impaired learning ability and the dietary DHA ameliorates this performance failure.     

An autopsy case of primary squamous cell carcinoma of the liver associated with hepatitis C virus antibody positive liver cirrhosis

An increase in potassium (K) intake may lower blood pressure (BP), but inconsistent results have been obtained in clinical trials. We studied the effects of K supplementation in hypertensive patients with monitoring of home and ambulatory BP. Fifty-five patients with essential hypertension (26 men, 29 women, 36-77 years old) participated in this study. A 4-week K supplementation period and 4-week control period were assigned in a randomized crossover manner. During the K period, the subjects were given 64 mmol/day of K as slow-release KCl tablets. Office, home, and 24-h BP, as well as serum and urinary electrolytes, were measured at the end of each period. In the control period, office, home, and 24-h BP were 151 +/- 2/88 +/- 1 (mean +/- SE), 138 +/- 1/83 +/- 1, and 137 +/- 1/81 +/- 1 mm Hg, respectively. Serum K increased from 4.15 +/- 0.04 to 4.42 +/- 0.05 mmol/L, and urinary K increased from 54 +/- 2 to 96 +/- 3 mmol/day with the K supplementation. Office, home, and 24-h BP were significantly lower in the K period than in the control period, although the differences were small (2.7 +/- 1.1/1.4 +/- 0.6, 3.6 +/- 0.9/1.7 +/- 0.5, 3.4 +/- 1.0/1.2 +/- 0.5 mm Hg, respectively). Changes in home and 24-h systolic BP with K supplementation were highly significant (P < .001), compared with office BP (P < .05). The change in 24-h systolic BP was correlated negatively with baseline BP and urinary Na/K ratio, and positively with baseline urinary K excretion. The changes in daytime and nighttime BP were comparable. These results indicate that increasing K intake lowers BP in hypertensive subjects, especially in those with higher BP and lower K intake. Our study supports the usefulness of K supplementation in the treatment of hypertension, although its antihypertensive effect may be small.     

The differentiation of DSM-III-R psychotic depression in later life from nonpsychotic depression: comparisons of brain changes measured by multispectral analysis of magnetic resonance brain images, neuropsychological findings, and clinical features

P2U/2Y-receptors elicit multiple signaling in Madin-Darby canine kidney (MDCK) cells, including a transient increase of [Ca2+]i, activation of phospholipases C (PLC) and A2 (PLA2), protein kinase C (PKC) and mitogen-activated protein kinase (MAPK). This study examines the involvement of these signaling pathways in the inhibition of Na+,K+,Cl- cotransport in MDCK cells by ATP. The level of ATP-induced inhibition of this carrier ( approximately 50% of control values) was insensitive to cholera and pertussis toxins, to the PKC inhibitor calphostin C, to the cyclic nucleotide-dependent protein kinase inhibitors, H-89 and H-8 as well as to the inhibitor of serine-threonine type 1 and 2A phosphoprotein phosphatases okadaic acid. ATP led to a transient increase of [Ca2+]i that was abolished by a chelator of Ca2+i, BAPTA. However, neither BAPTA nor the Ca2+ ionophore A231287, or an inhibitor of endoplasmic reticulum Ca2+-pump, thapsigargin, modified ATP-induced inhibition of Na+,K+, Cl- cotransport. An inhibitor of PLC, U73122, and an inhibitor of MAPK kinase (MEK), PD98059, blocked ATP-induced inositol-1,4, 5-triphosphate production and MAPK phosphorylation, respectively. However, these compounds did not modify the effect of ATP on Na+,K+, Cl- cotransport activity. Inhibitors of PLA2 (AACOCF3), cycloxygenase (indomethacin) and lypoxygenase (NDGA) as well as exogenous arachidonic acid also did not affect ATP-induced inhibition of Na+,K+,Cl- cotransport. Inhibition of the carrier by ATP persisted in the presence of inhibitors of epithelial Na+ channels (amiloride), Cl- channels (NPPB) and Na+/H+ exchanger (EIPA) and was insensitive to cell volume modulation in anisosmotic media and to depletion of cells with monovalent ions, thus ruling out the role of other ion transporters in purinoceptor-induced inhibition of Na+,K+,Cl- cotransport. Our data demonstrate that none of the known purinoceptor-stimulated signaling pathways mediate ATP-induced inhibition of Na+,K+,Cl- cotransport and suggest the presence of a novel P2-receptor-coupled signaling mechanism.     

Effects of maternal ageing and dietary antioxidant supplementation on ovulation, fertilisation and embryo development in vitro in the mouse

The present study aims to ascertain whether dietary supplementation with a mixture of vitamins C and E may prevent the maternal-age-associated decrease in both the number of ovulated oocytes after exogenous ovarian stimulation and embryo development in vitro in the mouse. Experimental females were fed a standard diet supplemented with i) high doses of vitamins C and E from the first day of weaning until 12 or 40 weeks of age; or ii) moderate doses of vitamins C and E from the first day of weaning until 12 weeks of age or from 22 to 33 weeks of age. The age-related reduction in ovulation rate was partially prevented by supplementing diet with high doses of vitamins C and E from the first day of weaning. Shorter periods of treatment and lower doses of vitamins C and E were also efficient in preventing the maternal-age-associated reduction in ovulation rate after exogenous ovarian stimulation. No effect of maternal diet on fertilisation and embryo development was observed until the blastocyst stage. Although any extrapolation to human fertility should be made with caution, these findings may have direct implications for preventing or delaying maternal-age-associated infertility in humans.     

Detailed examination of vascular lesions triggered by an inhibitor of endothelium-derived relaxing factor

BACKGROUND: Inhibition of an endothelium-derived relaxing factor (EDRF) may contribute to the pathogenesis of thrombotic arterial occlusions. EXPERIMENTAL DESIGN: We measured the blood pressure and urinary excretion of protein, sodium, and potassium and histologically examined the brains, hearts, and kidneys in normotensive Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) fed on a diet containing: (a) EDRF inhibitor (L-N-nitroarginine:L-NNA); (b) L-arginine, which reverses the effect of L-NNA; or (c) both L-NNA and L-arginine for 1 to 8 weeks. In addition, we examined L-NNA-treated SHRSP, the blood pressures of which were lowered using hydralazine. Furthermore, we produced and examined Goldblatt's renal hypertensive rats, which are of a different type from those resulting from the L-NNA treatment. RESULTS: Both WKY and SHRSP rats fed on a diet containing L-NNA suffered from hypertension and cerebral infarctions in a dose-dependent manner. Cerebral infarctions occurred whether or not SHRSP rats were treated with an antihypertensive agent when they were fed a high dosage of L-NNA. In contrast, SHRSP rats, treated simultaneously with both L-NNA and L-arginine, suffered few cerebral infarctions, although they were severely hypertensive. In addition, there were no cerebral infarctions in Goldblatt's renal hypertensive rats, although they suffered from advanced hypertension. CONCLUSIONS: The data indicate that the inhibition of EDRF injures the vessel walls and encourages platelet adhesion to the damaged areas. The adhering platelets narrow the lumen with resultant thrombotic arterial occlusions. Pathophysiologic conditions that decrease EDRF synthesis appear to play an important role in cerebral, renal, and myocardial infarctions.     

The effects of dietary sodium on the diurnal activity of the renin-angiotensin-aldosterone system and the excretion of urinary electrolytes

Diurnal variations of five normal men were tested over three 24 h consecutive periods. The first experiment began at 0900 h after the subjects had fasted for 12 h and a normal sodium diet of about 70-80 mEq was given at 0900 h, 1200h, and 1630 h (total of about 220 mEq of Na). Significant variations in the plasma renin activity (PRA), in the plasma aldosterone (PA), and in the urinary Na and K outputs were found. The second experiment began at 1200 h with the first feeding time at 2100 h after fasting about 24 h and the subjects were given a normal sodium diet as in the first experiment, but with the meals given at 2100 h, 2400 h, and 0430 h. The diurnal variations in PRA, plasma aldosterone, and urinary electrolytes disappeared. From this study, it appears that the diurnal variation in urinary electrolyte excretion is a factor of the diurnal variation in PRA and plasma aldosterone. The diurnal variation in PRA and plasma aldosterone are related to the timing of sodium ingestion.     

Cyclic AMP-dependent anion secretion in human small and large intestine

Cyclic AMP-dependent Cl- secretion is the major secretion pathway in human intestine. The aim of the present study was to examine mechanisms involved in cAMP-dependent anion secretion in human small and large intestine. Surgical resection specimens from both jejunum and distal colon were studied under short circuited conditions. Addition of the phosphodiesterase inhibitor IBMX induced an increase in the short-circuit current (Isc) equivalent to the net increase in Cl- secretion. The Isc was inhibited by diphenylamine decarboxylate (DPC; Cl- channel blocker), bumetanide (basolateral Na+/K+/2Cl- cotransporter), BaCl2 (basolateral K+ channel) and Cl- free buffer in both segments and indomethacin (cyclo-oxygenase inhibitor) in colon alone. Diphenylamine decarboxylate appears to directly inhibit secretion in jejunum, although its inhibitory effect is possibly mediated by inhibition of cyclo-oxygenase in the colon. A small component of IBMX-stimulated Isc was inhibited by acetazolamide. Cyclic AMP-dependent secretion is largely apical Cl- secretion, although a small component appears to be HCO3. Secretion is dependent on basolateral K+ channels and Na+/K+/2Cl- cotransporters and, in the colon, is inhibited by indomethacin, implying a role for cyclo-oxygenase metabolites. The chloride channel blocker DPC inhibits secretion in both areas. This class of compounds may have potential for treatment of secretory diarrhoea.     

Hospital charges for terminal care of cancer patients dying before age 65

The aim of this study was to determine whether the prevention of stroke with perindopril treatment in stroke-prone spontaneously hypertensive rats (SHRSP) is associated with the preservation of the myogenic properties of the cerebral arteries. After weaning at 4 weeks of age, male SHRSP were fed a Japanese-style rat diet with high salt to induce stroke development. Treatment with perindopril was given by gavage every morning beginning at 6 weeks of age. There were three experimental groups: two groups treated with 4 mg.kg-1.day-1 perindopril for different durations (8 or 12 weeks) and one control group consisting of littermates given distilled water. All the control animals developed stroke and died within 14 weeks of age, and myogenic response of the middle cerebral arteries (MCA) to pressure increase was lost in these animals. In contrast, all the treated SHRSP survived during the treatment period, and myogenic response of the MCA was preserved. After withdrawal of the treatment, SHRSP treated for a longer period (12 weeks) also survived longer than those treated for a shorter period (8 weeks). The subsequent development of stroke and death following treatment withdrawal after 8 or 12 weeks of treatment was associated with the loss of pressure-dependent constriction in MCA. A longer treatment duration also increased the stiffness of the MCA, MCA from SHRSP after 12 weeks of treatment had smaller external and lumen diameters, and thicker walls than those from the 8-week treatment group. In a separate study, we found that treatment of SHRSP with 1 or 4 mg.kg-1.day-1 of perindopril for 24 weeks beginning at 6 weeks of age also protected them against death related to stroke, because these rats survived up to 43 weeks of age, when the experiment was terminated. We conclude that there is an association between the absence of myogenic response in cerebral arteries and stroke development in SHRSP. Perindopril treatment preserves the myogenic response of MCA in SHRSP and prevents the stroke development in these animals. A prolonged treatment could increase the survival of SHRSP through a remodelling of the MCA and increasing the stiffness of the cerebral arteries.     

Immunohistochemical demonstration of spread of Aujeszky''s disease virus to the porcine central nervous system after intestinal inoculation

The effects of the non-mammalian tachykinin physalaemin were studied on the short circuit current (SCC) and on both influx (Ji) and outflux (Jo) of 36Cl- and 22Na+ across the isolated skin of Rana esculenta. Physalaemin, added to the internal bathing fluid, increased SCC in a dose-dependent manner with a maximal effect at 1 microM. This increase was due to a stimulation of both Na+ absorption and Cl- secretion. Bumetanide (20 microM in the internal fluid), an inhibitor of the Na+/K+/2Cl- cotransporter, reduced the action of physalaemin on SCC by 46%. Furthermore diphenylamine-2-carboxylic acid (DPC, 0.1 mM in the external fluid), an inhibitor of Cl- channels, decreased the effect of the peptide on SCC by 48%. It is concluded that physalaemin activates the Na+/K+/2Cl- cotransporter at the basolateral membrane, accumulating Cl- in the cells and favouring its exit through Cl- channels at the outermost membrane of the epithelium. An inhibitor of cyclooxygenases, i.e. naproxen, strongly inhibited the physalaemin effect on SCC, whereas 5,8,11-eicosatriynoic acid (ETI), an inhibitor of lipooxygenases was without effect. Therefore, it is proposed that prostaglandins (probably PGE2) are the cellular mediators of this action. An antagonist of NK1 receptors for tachykinins, CP 99,994, inhibited the physalaemin action on SCC, whereas challenge with SR 48,968, an antagonist of NK2 receptors, had no effect on physalaemin action. It is concluded that physalaemin effect on SCC in frog skin is mediated by its interaction with NK1 receptors.     

Osmoregulation and salinity effects on the expression and activity of Na+,K(+)-ATPase in the gills of European sea bass, Dicentrarchus labrax (L.)

The European sea bass, Dicentrarchus labrax, tolerates salinities ranging from freshwater (FW) to hypersaline conditions. In two experiments, we analysed changes in plasma ions, muscle water content (MWC), gill Na+,K(+)-ATPase activity, and alpha-subunit mRNA expression during the course of acclimation from 15 ppt salt water to FW or high salinity seawater (HSSW). In Experiment 1, fish (6.2 +/- 1.1 g) were acclimated from 15 ppt to either FW, 5, 15, 25, 50, or 60 ppt SW and sampled after 10 days. Gill Na+,K(+)-ATPase activity was stimulated in FW- and in 50 and 60 ppt SW-groups relative to the 15 ppt control group. In Experiment 2, subgroups of fish (89 +/- 7 g) were transferred from 15 ppt SW to FW or 50 ppt SW, and sampled 1, 2, 4, and 10 days later. Plasma osmolality, [Na+] and [Cl-] decreased in the FW-group and increased in the HSSW-group one day after transfer and lasting until day 10. This was accompanied by a pronounced increase in MWC in the FW-group and an insignificant decrease in the HSSW-group. The plasma [Na+]:[Cl-]-ratio increased markedly in the FW-group and decreased slightly in the HSSW-group, suggesting acid-base balance disturbances after transfer. Gill Na+,K(+)-ATPase activity was unchanged in 15 ppt SW but doubled in FW- and HSSW-groups after transfer. In both groups, this was preceded by a 2- to 5-fold elevation of the gill alpha-subunit Na+,K(+)-ATPase mRNA level. Thus increased expression of alpha-subunit mRNA is part of the molecular mechanism of both FW and SW acclimation in sea bass. Gill Na+,K(+)-ATPase Na(+)-, K(+)-, and ouabain-affinity were similar in fish acclimated to FW, 15 ppt, and HSSW, suggesting that identical isoforms of the catalytic subunit of the enzyme are expressed irrespective of salinity.     

Epidemiological study of hypertension and its determinants in an urban population of North India

OBJECTIVES: To determine age-specific prevalence of hypertension and blood pressure (BP) levels in relation to diet and lifestyle factors in North Indians. DESIGN AND SETTING: Cross-sectional survey in 20 randomly selected streets in Moradabad, North India. SUBJECTS AND METHODS: A total of 1806 subjects from North India (904 males and 902 females) age range 25-64 years. The survey methods were as follows: dietary diaries for 7 days food intake record; BP measurements; physician administered questionnaire and anthropometric measurements. Diagnosis of hypertension was based on new World Health Organization/International Society of Hypertension (WHO/ISH) criteria. Risk factors were assessed based on WHO guidelines. RESULTS: The prevalence of hypertension according to WHO/ISH criteria was 23.7% and by old WHO criteria 13.3%. In the WHO/ISH hypertensive group, isolated diastolic hypertension was present in 47.3% males and 40.6% females. Males have a slightly higher prevalence than females in the young age group, however, the prevalence rates are comparable in the older age groups. In both sexes, the prevalence rates and BP level increased with older age. Multivariate analysis revealed that age, higher body mass index, central obesity and higher socioeconomic status were independently and strongly associated with hypertension in both sexes. Higher dietary fat and salt intake and lower physical activity were weakly but significantly associated with hypertension. CONCLUSION: Association of higher socioeconmic status, higher body mass index and central obesity in North Indian adults with higher fat intake, lower physical activity and higher prevalence and level of hypertension indicate that these populations may benefit by decreasing the dietary fat intake and increasing physical activity, with an aim to decrease central obesity for decreasing hypertension in North Indians.     

Age and blood pressure related changes in cholesterol esterase activity and cholesterol content in aortas of stroke prone spontaneously hypertensive rats, spontaneously hypertensive rats and normotensive Wistar Kyoto rats

Changes in aortic lipolytic enzyme activities (cholesterol esterase and lipoprotein lipase) and acid phosphatase activity during aging were investigated in three strains of rats with different blood pressures; stroke prone spontaneously hypertensive rats (SHRSP), spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKR). The blood pressures of male, 7 month old animals, was 234 (SHRSP), 173 (SHR) and 128 (WKR) mmHg. The cholesterol esterase activity markedly decreased with age in the aortas of SHRSP, SHR and normotensive WKR rats, while acid phosphatase activity decreased only slightly, if at all, and lipoprotein lipase activity remained unchanged. This effect was enhanced by increasing blood pressure in SHRSP, SHR and WKR. The total aortic cholesterol content increased significantly with hypertension in a inverse relation with cholesterol esterase activity. These results suggest that cholesterol deposition in aged arteries is, at least partialy, ascribable to an age-related decrease in cholesterol esterase, and that hypertension aggravates the deposition of arterial cholesterol by accelerating the age-related decrease in aortic cholesterol esterase activity.     

Effect of anionic salts in prepartum diets based on alfalfa

This study compared prepartum diets based on grass, alfalfa, or alfalfa and anionic salts to investigate their effect on Ca metabolism, acid-base status, endocrine response, disease incidence, and lactational performance of periparturient dairy cows. Forty-five nonlactating Holstein cows in their last 3 wk of gestation were fed a control diet based on grass hay with a dietary cation-anion difference [expressed as milli-equivalents of ((Na + K) - (Cl + S))/100 g of dietary dry matter] of +30 or diets based on alfalfa with a dietary cation-anion difference of either +35 or -7. Cows fed the diet with the dietary cation-anion difference of -7 had the lowest urine pH prepartum and had the highest concentrations of ionized Ca in blood and total Ca in serum at parturition. Increases in 1,25-(OH)2 vitamin D per unit decrease in total Ca in serum were greatest for cows fed the diet with a dietary cation-anion difference of -7. Also, cows fed this same diet consumed the most dry matter postpartum. Incidences of health disorders were 13% (10 of 75), 12% (9 of 75), and 5% (4 of 75) for cows fed the diets with dietary cation-anion differences of +30, +35, and -7, respectively. Results indicate that alfalfa, when supplemented with anionic salts, is a viable forage for prepartum dairy cows.