Aldosterone secretion during high sodium cerebrospinal fluid perfusion of the brain ventricles

Conscious sheep with permanent indwelling cannulae in the lateral ventricles and the cisterna magna were Na depleted and then perfused for 9 h with an artificial CSF solution. There were 3 experimental groups: Group I (n=5) received perfusion with aritifical CSF containing NA 170 MEq./1, Group II (n=7) received perfusion with artificial CSF containing Na 145 mEq./1, Group III (n=7) received no perfusion. In Group I the blood aldosterone level fell from 26.4 +/- 7.4 to 8.6 +/- 2.3 ng/100 ml by 9 h after perfusion. There was no significant change in plasma [Na] or [K], blood angiotensin II or plasma renin concentration. Blood cortisol and corticosterone levels rose. There was also a fall in post-perfusion. Group III showed no significant change in blood aldosterone concentration. Multivariate statistical analysis showed that the fall in aldosterone levels during 170 mEq./l Na perfusion could not be accounted for by changes, either alone or together, of ACTH as evidenced by alteration in blood cortisol or corticosterone, or by change of plasma [Na], [K] or renin concentrations. This data supports the hypothesis of an additional factor which may be of CNS origin being involved in the control of aldosterone secretion.     

Effects of coenzyme Q on plasma aldosterone concentrations in dogs (author's transl)

The renin-angiotensin system, potassium and adrenocorticotropin (ACTH) are well known as control mechanism for aldosterone secretion. However, the precise mechanism of these factors for aldosterone secretion remain still unclear. Several interesting evidences related to the effects of Coenzyme Q on the secretion and biosynthesis of aldosterone have been demonstrated. Biochemical action of Coenzyme Q is generally accepted as a component of the electron transfer process of respiration in mitochondria. Fabre et al demonstrated that significant reduction of plasma aldosterone concentration in adrenal venous by the Coenzyme Q infusion. Weinstein et al observed that urine sodium excretion decreased after infusion of Coenzyme Q into renal artery. Kumagai et al suggested that Coenzyme Q inhibited the activity of 18-hydroxylase in the adrenal cortex. The present study was designed to evaluate the effects of Coenzyme Q on the secretion of aldosterone. Method: 24 cases of male among el and beagle dogs were subdivided into 4 groups. 1st group were administered intravenous infusion of Coenzyme Q, 2nd group were orally administered Coenzyme Q for 7 weeks, 3rd group were administered simultaneous infusion of Coenzyme Q and angiotensin II and 4th group were administered furosemide orally under the condition of continuous Coenzyme Q administration. Then, plasma concentrations of aldosterone, 11-OHCS and angiotensin I were determined during the time course. Results and Discussions: Plasma aldosterone concentration was significantly increased after intravenous infusion of angiotensin II and decreased 45 minutes after the beginning of infusion. However, the concentration still remained higher than control level. By the simultaneous infusion of Coenzyme Q with angiotensin II, the decreased concentration again increased significantly. It seems that above mentioned results suggest possibility that Coenzyme Q potentiate the action of angiotensin II on aldosterone secretion. By the intravenous infusion of Coenzyme Q, plasma aldosterone concentration increased significantly and concentrations of plasma 11-OHCS and angiotensin I did not affected. This result suggests that Coenzyme Q may stimulate aldosterone secretion from adrenal cortex without increase of ACTH and renin-angiotensin. 4 hours after the oral administration of Coenzyme Q, plasma aldosterone concentration was increased significantly. Na/K in 24 hours' excreta was decreased by Coenzyme Q administration. The decrease of Na/K in excreta may be reflection of the increase of aldosterone secretion. Although, plasma aldosterone concentration increased for the short duration by the Coenzyme Q, it decreased gradually and returned to the control level after 7 days under the condition of continuous oral administration. By the oral administration of furosemide under prolonged Coenzyme Q administration plasma aldosterone concentration increased significantly and remained higher than that of control.     

Effect of administered potassium on the renin-aldosterone axis in young blacks compared with whites

BACKGROUND: We had observed previously that the aldosterone excretion rate and plasma aldosterone concentration were lower for black children than they were for white children. We did not know whether this was secondary to a lower intake of potassium or to suppression of the renin-angiotensin system in blacks. OBJECTIVE: To test the hypothesis that the secretion of aldosterone in response to potassium would be different in blacks than in a control group of whites. DESIGN: Black and white subjects were selected on the basis of their having aldosterone excretion rates that were in the lowest quartile for the entire original cohort. Since the blacks typically had lower aldosterone excretion rates than did the whites, the black participants were represented primarily by those with average rates of aldosterone production among blacks, whereas the whites were represented by those with the lowest aldosterone production rates among whites. The protocol consisted of a placebo-controlled, randomized cross-over study design. METHODS: Twelve blacks and 12 whites, aged 14.1 +/- 1.6 (mean +/- SD) and 15.4 +/- 2.1 years, respectively, were allocated randomly to double-blind treatment either with placebo or with 40 mmol/day potassium chloride for 7 days and then the alternate treatment Measurements of the plasma renin activity (PRA), plasma aldosterone concentration, and urinary aldosterone excretion were performed in an inpatient research unit at the end of the treatment. The blood pressure was monitored for 24 h. RESULTS: Treatment with potassium increased the plasma aldosterone concentration (P = 0.0006) and the urinary excretion of aldosterone (P = 0.0002) significantly both for blacks and for whites. There was no significant racial difference in the response to potassium. The PRA was overall 1.605-fold lower in the blacks than it was in the whites (P = 0.0124). The lowest PRA levels, such as those in the blacks when they were supine, tended to be increased with the potassium treatment. The blood pressure did not change significantly with the potassium supplement for either racial group. CONCLUSIONS: After we had supplemented the intake of potassium, aldosterone production increased in the blacks and in the control group of whites to the same extent The potassium treatment appeared to increase lower PRA levels. A lower intake of potassium could at least partially account for the suppression of the renin-aldosterone system in blacks.     

The erythrocyte Na,K,Cl cotransporter and its circulating inhibitor in Dahl salt-sensitive rats

BACKGROUND: Abnormal Na,K,Cl cotransport is thought to be a pathogenic factor in Dahl salt-sensitive rat models, but the only direct evidence for this is an increased cotransport activity found in erythrocytes from salt-loaded Dahl salt-sensitive rats. OBJECTIVE: To re-examine erythrocyte cotransport fluxes and a circulating cotransport inhibitory factor (CIF) in inbred Dahl rats maintained on a low (0.2%) salt diet. Cotransport fluxes were investigated both under basal conditions and after stimulation by cell shrinking. METHODS: Blood was drawn from 12 male Dahl salt-sensitive and 12 Dahl salt-resistant rats of the inbred John Rapp strain. Erythrocyte Na,K,Cl cotransport activity was equated to the bumetanide-sensitive fluxes of sodium, rubidium or lithium. Plasma CIF activity was tested in human erythrocytes. RESULTS: In Dahl salt-sensitive rats: (1) plasma CIF activity (5.7+/-0.4 units/ml) was modestly higher than in Dahl salt-resistant rats (2.97+/-0.12 units/ml, P < 0.0001), but much lower than that previously found in salt-loaded Dahl salt-sensitive rats (16.1 units/ml), and (2) erythrocytes exhibited a similar bumetanide-sensitive sodium efflux (rate constant 0.056+/-0.008 h(-1)) as in Dahl salt-resistant rats (0.047+/-0.007 h(-1)). Following hypertonic shock, the bumetanide-sensitive rubidium influx reacted more to cell shrinkage in Dahl salt-sensitive than in Dahl salt-resistant erythrocytes (cell volume decrease required to stimulate bumetanide-sensitive rubidium influx by 4000 micromol/l cells per h=-4.04+/-0.36 versus -5.89+/-0.44 fl, respectively; P< 0.01). CONCLUSIONS: When fed a low-salt diet, Dahl salt-sensitive rats present slightly increased plasma CIF levels and normal erythrocyte cotransport fluxes under basal conditions, but an increased response to a hypertonic shock. Therefore, if there is any primary cotransport abnormality in Dahl salt-sensitive rats, it appears to be restricted to the renal Na,K,Cl cotransporter BSC1 isoform. Alternatively, any such change may be the consequence of abnormal regulation by osmolarity-dependent mechanisms.     

Losartan and angiotensin II inhibit aldosterone production in anephric rats via different actions on the intraadrenal renin-angiotensin system

Angiotensin II (ANG II) is a major stimulator of aldosterone biosynthesis. When investigating the relative contribution of circulating and locally produced ANG II, we were therefore surprised to find that ANG II, given chronically s.c. (200 ng/kg x min), markedly inhibits a nephrectomy (NX)-induced rise of aldosterone concentrations (from 10 +/- 2 to 465 +/- 90 ng/100 ml in vehicle infused, and from 9 +/- 2 to 177 +/- 35 in ANG II infused rats 55 h after NX and hemodialysis). We further observed, by in situ hybridization, that bilateral NX increases the number of adrenocortical cells expressing renin and that this rise was prevented by ANG II. Moreover, the rise of aldosterone levels was also inhibited by the AT1-receptor antagonist, losartan (10 microg/kg x min, chronically i.p. from 8 +/- 2 to 199 +/- 26 ng/100 ml), despite the absence of circulating renin and a reduction of ANG I to less than 10%. These data demonstrate that aldosterone production, after NX, is regulated by an intraadrenal renin-angiotensin system and that this system is physiologically suppressed by circulating angiotensin. Because the effects of losartan or ANG II on aldosterone production involved a latency period of at least 30 h after NX and were associated with a modulation or recruitment of renin-producing cells, we suggest that the intraadrenal renin-angiotensin system operates via regulation of cell differentiation on a long-term scale, rather than or additionally to its short-term effects on aldosterone synthase activity.     

Effects of dietary salt restriction on blood pressure and the renal vasoactive system in the congenitally bilateral hydronephrotic rat

We examined the responses on blood pressure when the renal vasoactive system such as renin-angiotensin-aldosterone system (RAAS) and kallikrein-kinin system (KKS) was activated by dietary salt restriction in the congenitally bilateral hydronephrotic rat (BHN). In a low salt diet (LS)-normotensive and normal kidney control rats after 8 weeks from initiating dietary salt restriction, the plasma sodium concentration (PNa) was retained at a level similar to that in the normal diet (ND)-control rats, and plasma renin activity (PRA), plasma aldosterone concentration (PAC) and urinary kallikrein activity (UKA) were about 1.8-, 9.4-and 1.7-fold higher, respectively, than those in the ND-control rats. In addition, LS-control rats had a significantly (p < 0.001) high systolic blood pressure (163 +/- 2.0 mm Hg) compared with that (136 +/- 5.8) of ND-control rats. These results suggest that the activated renal vasoactive system acted for not only sodium retention but also for elevation of blood pressure in LS-control rats. In LS-BHN at week 8, PNa was also retained at a nearly normal level. However, the renal vasoactive system activation for sodium retention was higher than that of LS-control rats; that is, increase of PRA, PAC and UKA were about 3.8-, 24.7-and 10.0-fold, respectively, than in ND-BHN. The higher activation of RAAS, nevertheless, does not affect blood pressure in BHN; that is, both hypertension of BHN fed LS and ND developed similarly. These findings suggest that dietary salt restriction could markedly activate the renal vasoactive system for sodium retention without elevating blood pressure in BHN different from control rats.     

Hormonal control of water and sodium in plasma and urine of camels during dehydration and rehydration

Eight dromedary camels were studied for 24 days under control conditions (3 days), and during water deprivation (14 days) and rehydration (7 days) in Tadla (Morocco), during the summer. During dehydration, food intake gradually fell and was zero on the last day and animals lost about 30% of their body weight. However, most of this reduction in weight was attributed to water loss, since body weight of the animals returned to control values following rehydration. Dehydration was associated with a decrease in plasma volume (-42 +/- 3%) and a concomitant rise in plasma Na concentration (from 154 +/- 2 to 191 +/- 3 mM). These changes were accompanied by increased plasma arginine-vasopressin (from 0.2 +/- 0.1 to 5.7 +/- 2.2 pg ml-1) and plasma renin activity (from 1.2 +/- 0.2 to 20.0 +/- 5.2 ng Al ml-1 hr-1), without significantly changed plasma concentrations of aldosterone and atrial natriuretic peptide. Dehydration was associated with increased urine osmolality (from 952 +/- 515 to 1963 +/- 498 mosm kg-1 H2O), reduced urine production (from 4565 +/- 2230 to 817 +/- 178 ml day-1), and increased Na excretion. Most of these parameters returned to control values during initial rehydration, except for plasma renin activity, which remained elevated for 7 days, and diuresis, which rose to 12773 +/- 6707 ml day-1 on Day 7 of rehydration.     

Losartan blocks aldosterone and renal vascular responses to angiotensin II in humans

In vitro and animal studies have demonstrated that the effect of angiotensin II (Ang II) on aldosterone is mediated through the Ang II type 1 receptor. However, it has been difficult to demonstrate an effect of Ang II type 1 receptor blockade on aldosterone levels in human studies. One possible explanation is that subjects have not been studied under salt-controlled conditions. Therefore, we examined the effects of losartan on the aldosterone and renal plasma flow responses to Ang II infusion in six normotensive subjects under low and high salt conditions. Ang II was infused in graded doses (0.3 to 10 ng/kg per minute) in the presence and absence of losartan (a single 50-mg oral dose). Renal plasma flow was assessed by measurement of para-aminohippurate clearance. Blood pressure, plasma aldosterone levels (low salt conditions only), and para-aminohippurate clearance were measured before and after each Ang II dose. Losartan had no effect on baseline systolic pressure but attenuated the systolic pressure response to exogenous Ang II during both low salt (0.7 +/- 1.9 versus 6.7 +/- 1.4 mm Hg, P = .001) and high salt (2.0 +/- 1.9 versus 12.3 +/- 2.1 mm Hg, P = .006) conditions. Under low salt conditions, losartan reduced the baseline plasma aldosterone level from 1135 +/- 204 to 558 +/- 102 pmol/L (P = .015) and blocked the aldosterone response to Ang II (-49 +/- 110 versus +436 +/- 83 pmol/L, P = .019). During high salt conditions, losartan had no effect on baseline renal plasma flow but attenuated the renal plasma flow response to Ang II (-90.1 +/- 15.1 versus -185.1 +/- 2.6 mL/min per 1.73 m2, P = .013). These data confirm that losartan lowers both basal and exogenous Ang II-stimulated aldosterone levels under low salt conditions. Losartan does not significantly affect baseline renal plasma flow but does attenuate the renal plasma flow response to exogenous Ang II under high salt conditions.     

Release of ouabain-like compound (OLC) from the intact perfused rat adrenal gland

The present study was designed to investigate the effect of ACTH on release of OLC from the intact isolated rat adrenal, perfused in situ. OLC was measured by EIA. The limit of detection of the assay was 23 pmol/10 minutes. Basal levels of OLC varied from 240 to <23 pmol/10 min. Basal corticosterone levels were generally higher than OLC while aldosterone were generally lower. In 3 of the 5 perfusions the addition of ACTH was followed by rapid increases in both OLC and corticosterone secretion rates within 10 minutes of stimulation. Stimulated levels of OLC were 2 to 4-fold and of corticosterone were 3 to 7-fold those found in basal samples. OLC was found to co-elute with authentic ouabain under isocratic HPLC analysis whilst perfusion medium itself contained no detectable OLC immunoreactivity. These preliminary data suggest that the intact perfused rat adrenal preparation is a useful model for investigating the acute regulation of OLC secretion.     

Tonic inhibition of renin secretion by the 12 lipoxygenase pathway: augmentation by high salt intake

Recent evidence suggests that lipoxygenase (LO) metabolites inhibit renin production in vitro. However, the physiological significance of this effect has not been determined. This study examined the role of the LO pathway in the regulation of plasma renin concentration (PRC) in vivo. The acute administration of two structurally unrelated LO inhibitors, phenidone (30 and 60 mg/kg) and esculetin (60 mg/kg), resulted in suppression of platelet 12 hydroxyeicosatetraenoic acid (12HETE) production, reduction in systemic arterial pressure and a 2- to 3-fold increase in PRC. To determine whether the esculetin-induced increase in PRC was secondary to hypotension, esculetin was also administered to rats preinfused with a pressor dose of norepinephrine. In these acutely hypertensive rats, esculetin still induced a 2.5-fold increase in PRC, whereas blood pressure remained over 40 mm Hg above basal levels. Further, esculetin (10(-6)M) increased renin release in renal slices from 150 +/- 10 to 310 +/- 20 ng/ml.h (P < 0.05) and this rise was entirely blocked in the presence of 12HETE (10(-7)M; 130 +/- 40 ng/ml.h). In rats placed on high salt intake, 12HETE concentration in renal slices from the outer cortex was considerably higher than in renal slices from salt-restricted rats (116.5 +/- 15.7 vs. 65 +/- 12 pg/mg protein; P < 0.05). Chronic administration of the LO inhibitor phenidone also resulted in an increase of PRC, which was independent of changes in blood pressure. On either high salt (3.15%0 or low salt (0.05%) diet phenidone-treated rats had higher PRC levels than the respective control groups [high salt 9.7 +/- 3.5 vs. 1.9 +/- 1.4 ng/ml.h; P < 0.05; low salt 33.2 +/- 5.3 vs. 19.4 +/- 3.10 ng/ml.h; P < 0.05]. The finding that LO blockers are potent stimulators of PRC in vivo suggests the existence of a physiological tonic inhibition of renin secretion by LO products that is operative under a wide range of salt intake. High salt intake enhances this inhibitory tone by increasing renal cortical 12 LO activity and, in fact, normal suppression of PRC during high salt diet does not occur in LO-blocked animals. Thus, the LO pathway exerts a tonic inhibitory effect on renin release, which appears particularly important for renin suppression during high salt intake.     

Evaluation of radioimmunological methods for assay of plasma and urinary aldosterone

Two radioimmunological methods for assay of plasma and urinary aldosterone were carefully evaluated. In the plasma method a radioimmunoassay is preceded by chromatography on a Sephadex LH-20 column. The method for urine includes a preextraction, hydrolysis of the acid-labile conjugates of aldosterone, and a radioimmunoassay. Both methods fulfill the criteria of reliability and are suitable for both routine and demanding research assays. The plasma method, using columns of double length, is also applicable to analysis of aldosterone in plasma of newborn children, and pregnant females and in cord plasma. The concentration of plasma aldosterone in healthy subjects on an ad lib salt diet was 162 +/- 93 (S.D.) pmol/1 in the supine position and 312 +/- 217 (S.D.) pmol/1 upright. The urinary excretion of aldosterone in healthy subjects was 28.3 +/- 16.7 (S.D.) nmol/24 h.     

Genetic analysis of renin gene expression in rat adrenal gland

We examined the mechanism of the increased renin mRNA concentration in the adrenal glands of spontaneously hypertensive rats (SHR). In 52 female F2 rats (25 to 27 weeks of age) derived from SHR and Wistar-Kyoto rats, we determined blood pressure, renin mRNA concentration in the adrenal gland, plasma renin activity, plasma aldosterone concentration, and genotype of the renin gene. Eighteen of the F2 rats were fed a high salt (8%) diet for 14 days. The renin mRNA concentration in the adrenal glands showed a significant correlation with the genotype of the renin gene in the normal salt diet group (P <.0001), whereas this relationship was not observed in the high salt group. Multivariate analysis revealed that the plasma aldosterone concentration in the normal diet group was significantly explained (P=.0004, R2=.454) by plasma renin activity (P=.0005), the renin mRNA concentration in the adrenal gland (P=.0496), and the genotype of the renin gene (P=.0236). The SHR allele of the renin gene was associated with a lower aldosterone concentration. On the other hand, in the high salt diet group, only the genotype of the renin gene showed a significant relationship with plasma aldosterone concentration (P=.0237). Again, the SHR allele of the renin gene was associated with a lower aldosterone concentration. We can conclude that the higher renin mRNA concentration in the SHR adrenal glands is governed by the SHR allele of the renin gene or renin gene locus. The renin mRNA concentration in the adrenal gland exerts a minor influence on aldosterone synthesis. Paradoxically, the SHR allele of the renin gene or renin gene locus confers a lower rate of aldosterone synthesis at 25 to 27 weeks of age, the mechanism of which remains to be determined.     

A prospective study of omeprazole suspension to prevent clinically significant gastrointestinal bleeding from stress ulcers in mechanically ventilated trauma patients

We recently reported that administration of Nomega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) production, activates the vascular and cardiac renin-angiotensin systems and causes vascular thickening and myocardial hypertrophy in rats with perivascular and myocardial fibrosis. It has been reported that aldosterone may contribute to the development of cardiac fibrosis, but it is not known whether inhibition of NO synthesis affects angiotensin II (Ang II) receptor gene expression and aldosterone secretion. The aim of this study was to investigate the effect of NO inhibition on the expression of Ang II receptors in the adrenal gland and on aldosterone secretion in rats. Wistar King A rats received normal water, L-NAME alone (1 mg/mL in the drinking water), or L-NAME and the alpha1-adrenergic receptor blocker bunazosin (0.1 mg/mL in the drinking water) for 1 week. After 1 week of treatment with L-NAME, systolic blood pressure, plasma aldosterone concentration (PAC), and mRNA level and number of Ang II type 1 receptor (AT1-R) were increased. Plasma renin activity, serum angiotensin-converting enzyme activity, and the number of AT2-R were unchanged. Although addition of bunazosin to L-NAME restored systolic blood pressure to the control level, PAC and AT1-R numbers remained significantly higher than those of control level. These results suggest that the increased AT1-R number and PAC induced by the inhibition of NO synthesis were independent of blood pressure and systemic renin-angiotensin system. Therefore, hypertension and myocardial fibrosis induced by NO blockade may be due in part to an elevation of PAC caused by increased AT1-R in the adrenal gland.     

Ethanol-induced changes in plasma proteins, angiotensin II, and salt appetite in rats.

Sodium depletion in rats elicits a sodium appetite that results from a cerebral action of angiotensin II (ANG II) and aldosterone. Alcohol also activates the renin-angiotensin system, but the mechanism is poorly understood and not related to sodium excretion. In this study, 2.5 g/kg intraperitoneal/ly (ip) ethanol produced a 20% decline in plasma volume and plasma protein concentration 1–2 hrs and elicited salt appetite beginning in 3–4 hrs. Blockade of ANG II synthesis in the brain and periphery with the angiotensin-converting enzyme inhibitor captopril eliminated the thirst and salt appetite. Peripheral captopril alone enhanced fluid intake, which indicated that alcohol elevated renin secretion. Ethanol-induced suppression of hepatic plasma protein secretion and the consequent fall in plasma colloid osmotic pressure apparently resulted in hypovolemia and renin secretion, which then produced thirst and salt appetite through an action of ANG II on the brain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid activation of Na+/H+ exchange by aldosterone in renal epithelial cells requires Ca2+ and stimulation of a plasma membrane proton conductance

There is increasing evidence for an additional acute, nongenomic action of the mineralocorticoid hormone aldosterone on renal epithelial cells, leading to a two-step model of mineralocorticoid action on electrolyte excretion. We investigated the acute effect of aldosterone on intracellular free Ca2+ and on intracellular pH in an aldosterone-sensitive Madin-Darby canine kidney cell clone. Within seconds of application of aldosterone, but not of the glucocorticoid hydrocortisone, there was a 3-fold sustained increase of intracellular Ca2+ at a half-maximal concentration of 10(-10) mol/liter. Omission of extracellular Ca2+ prevented this hormone response. In the presence of extracellular Ca2+ aldosterone led to intracellular alkalinization. The Na+/H+ exchange inhibitor ethyl-isopropanol-amiloride (EIPA) prevented the aldosterone-induced alkalinization but not the aldosterone-induced increase of intracellular Ca2+. Omission of extracellular Ca2+ also prevented aldosterone-induced alkalinization. Instead, aldosterone led to a Zn(2+)-dependent intracellular acidification in the presence of EIPA, indicative of an increase of plasma membrane proton conductance. Under control conditions, Zn2+ prevented the aldosterone-induced alkalinization completely. We conclude that aldosterone stimulated net-entry of Ca2+ from the extracellular compartment and a plasma membrane H+ conductance as prerequisites for the stimulation of plasma membrane Na+/H+ exchange which in turn modulates K+ channel acitivity. It is probable that the aldosterone-sensitive H+ conductance maintains Na+/H+ exchange activity by providing an acidic environment in the vicinity of the exchanger. Thus, genomic action of aldosterone determines cellular transport equipment, whereas the nongenomic action regulates transporter activity that requires responses within seconds or minutes, which explains the rapid effects on electrolyte excretion.     

Low Na+ diet inhibits Na+ and water transport response to vasopressin in rat cortical collecting duct

BACKGROUND: We previously demonstrated that vasopressin (AVP) produces a sustained increase in Na+ reabsorption by the isolated perfused cortical collecting duct (CCD) from rats on a normal diet, and that this effect is synergistic with that of pharmacological doses of deoxycorticosterone (DOC) or physiological levels of aldosterone. The present experiments examined the effect of AVP under the more physiological circumstances when plasma aldosterone was elevated by prior volume depletion. METHODS: Rats were volume depleted by a single dose of furosemide followed by a low-salt diet (0.3% NaCl) for four to nine days. Some of these rats were also implanted with a pellet containing 2.5 mg DOC. Rats in a third group were not injected with furosemide but were implanted with the DOC pellet and maintained on a standard (approximately 1% NaCl) diet. CCD were perfused and the lumen-to-bath Na+ flux (JNA), transepithelial voltage (VT), and osmotic water permeability (Pf) were measured in the presence and absence of 200 pm AVP. RESULTS: Although Na+ depletion by a single injection of furosemide and the low salt diet elevated plasma aldosterone and Vt, JNA remained low and there was a decreased response to AVP in comparison with DOC-treated rats on a standard diet. In CCD from rats on the low salt-diet with DOC, JNa was less than observed in CCD from DOC-treated rats on a standard diet. AVP-dependent Pf in CCD from rats on the low salt-diet, with or without DOC treatment, was also markedly lower. CONCLUSIONS: We interpret the results to demonstrate that maximal rates of Na+ reabsorption in the CCD depend not only on the synergistic stimulatory effects of aldosterone and AVP, but also require normal to high rates of salt delivery in vivo for the effects of the hormones on Na+ transport to be maximized in vitro.     

Small changes in extracellular sodium influence myogenic tone in rabbit facial vein by changing its sensitivity to calcium

Extracellular Na+ concentration ([Na+]e) significantly effects the regulation of myogenic tone in isolated blood vessels. We examined the effect of small changes in [Na+]e on simultaneous changes in stretch-activated myogenic tone in rabbit facial vein and 45Ca2+ unidirectional influx and net uptake. Decreasing [Na+]e from 150 to 120 mmol/l augmented myogenic tone (control: 3.15 +/- 0.27 mN, n = 22) by 89 +/- 29%, while raising [Na+]e to 165 mmol/l attenuated myogenic tone to 80 +/- 2% of control. Changes in myogenic tone induced by alterations in [Na+]e were not accompanied by proportional changes in 45Ca2+ net uptake. 45Ca2+ unidirectional influx per unit of wall force (10.2 +/- 1.0 pmol/mg per mN force, n = 22, control) was decreased to 6.1 +/- 0.6 pmol/mg per mN (n = 20, P < 0.05) and increased to 21.0 +/- 2.5 pmol/mg per mN (n = 14, P < 0.05) when [Na+]e was 120 or 165 mmol/l, respectively, suggesting that decreasing [Na+]e is related to an increased sensitivity to calcium. We conclude that, in the rabbit facial vein, the sensitivity of myogenic tone to changes in [Na+]e may reflect changes in the sensitivity of smooth muscle to Ca2+ through a change in mechanoreceptor sensitivity.     

Effects of aging on the regulation of intracellular pH in the rat jejunum

Jejunal villus cells from young-adult (6 months) and senescent (24 months) male Wistar rats were studied to evaluate the effect of aging on intracellular pH (pHi) regulation. pHi was measured by quantitative fluorescence microscopy by using BCECF-AM [2',7'-bis(carboxyethyl)-5(6)-carboxy-fluorescein acetoxy methylester] under basal conditions and after inducing cytoplasmic acidification with pulsed NH4Cl. In the senescent rats, the recovery rate from the acidified levels was significantly lower than that in the young-adult rats (.208 +/- .005 vs .255 +/- .004 pH units/min). The relationship between pHi recovery and external Na+ concentration followed Michaelis-Menten type kinetics, the maximum velocity (Vmax) of alkalinization being significantly lower in the senescent rats than in the young-adult rats (.227 +/- .033 vs .297 +/- .024 pH units/min). These results indicate that the recovery of pHi from an acidic level was slower in the senescent rats, due to the reduced activity of Na+/H+ exchange as revealed by the decreased Vmax value.     

Atrial natriuretic peptide metabolism during pregnancy in the rat

OBJECTIVE: Our purpose was to determine whether plasma clearance rates and production rates of atrial natriuretic peptide 99-126 are altered during pregnancy in the rat. STUDY DESIGN: Twelve virgin and 12 late-pregnant chronically instrumented, conscious, unrestrained Sprague-Dawley rats were studied. Mean arterial pressure, heart rate, and plasma atrial natriuretic peptide levels were measured before and during a 40-minute continuous infusion of atrial natriuretic peptide (10 ng/kg/min). RESULTS: Control mean arterial pressure was 106 +/- 5 mm Hg in virgin rats versus 97 +/- 4 mm Hg in pregnant rats. Atrial natriuretic peptide infusion did not significantly affect mean arterial pressure in either group of animals but decreased heart rate in virgin rats. Basal plasma atrial natriuretic peptide levels were significantly higher in virgin than in pregnant rats (107 +/- 10 vs 78 +/- 7 pg/ml, respectively, p < 0.05). Atrial natriuretic peptide infusion significantly increased plasma levels in both groups to similar (183 +/- 19 and 154 +/- 14 pg/ml, virgin vs pregnant rats). Calculated plasma clearance rates were similar in virgin and pregnant rats (166 +/- 27 vs 155 +/- 17 ml/kg/min). Estimated production rates of atrial natriuretic peptide were higher in virgin then in pregnant rats (15.1 +/- 1.4 vs 11.4 +/- 1.1 ng/kg/min, p < 0.05). CONCLUSIONS: Plasma atrial natriuretic peptide levels are lower in chronically instrumented near-term pregnant rats compared with levels in virgin rats. This is not related to differences in plasma atrial natriuretic peptide clearance rates but rather to a decrease in production rates in late pregnancy.