An evaluation of antiseptics used for hand disinfection in wards

The diurnal rhythm of plasma aldosterone concentration (PA), plasma renin activity (PRA), plasma cortisol (PC) and serum growth hormone (GH) were examined in 5 cases of normotensive acromegaly and the results were compared with the observations in normal subjects. Moreover, the response of PA to angiotensin-II infusion was studied in 6 cases of normotensive acromegaly. A normal diurnal rhythm with the lowest values in the evening or midnight and the highest values in the morning was observed in 3 of 5 cases in PA and 3 of 4 cases in PC. On the other hand, no apparent rhythm of GH was observed in any cases and that of PRA in 4 of 5 cases. Although there was a significant positive correlation between PA and PC, no significant correlation was demonstrated between PA and PRA. The response of PA to angiotensin-II fusion was significantly suppressed in normotensive acromegaly as compared to the normal subjects in spite of normal levels of PRA except for 1 case. The above observations were interpreted to suggest that the aldosterone regulation system is slightly altered in a certain number of patients with normotensive acromegaly in contrast to the normal subjects in which PRA is the main contributing factor. The low PA and suppressed response of PA toangiotensin-II infusion may suggest the defective action of angiotensin-II infusion on the adrenal gland.     

Effect of atrial natriuretic hormone on hypertonic saline-induced suppression of the renin-aldosterone system

To evaluate the effect of physiologic doses of atrial natriuretic hormone (ANH) on hypertonic saline-induced renin-aldosterone system suppression, nine healthy subjects were studied three times: 1) on a low-salt (LS) diet with a 2 h placebo infusion; 2) on LS with 2 h infusion of human Ser-Tyr28 ANH (0.6 pmol/kg/min)(LS+ANH); and 3) on a high-salt (HS) diet with a 2 h placebo infusion. On each study day during the second hour of infusion, subjects also received 3% saline (0.1 mL/kg/min) infusion. Data from eight subjects were used for analysis because of a sampling error in one subject. During ANH infusion, plasma ANH levels increased about twofold and reached levels similar to ANH levels on HS. Serum sodium increased by 3-4 mEq/L, and serum osmolality increased by 7-8 mOsm/L during 3% saline infusion on all study days. ANH levels remained stable during 3% saline infusion. During the first hour of ANH infusion, plasma renin activity (PRA) decreased by about 24% and aldosterone levels by about 27%. Hypertonic saline caused further suppression of PRA and aldosterone. The extent of the suppression was similar under each condition, and the levels at the end of hypertonic saline infusion reached about 60% of the levels at the beginning of the saline infusion. We conclude that low-dose ANH infusion does not seem to have any major influence on PRA and aldosterone response to hypertonic saline.     

Effect of blockade of angiotensin II on blood pressure, renin and aldosterone in cirrhosis

1-Sar-8-ala angiotensin II (saralasin) was infused intravenously in graded doses of from 0.1 to 10 mug/kg/min to five patients with cirrhosis and ascites after three days of restricted sodium intake. In each patient blockade of AII by saralasin produced a marked fall in blood pressure, a rise in plasma renin activity (PRA) and plasma renin concentration (PRC) and, in four of the five, a fall in plasma aldosterone (PA). The rise in PRA and PRC correlated poorly with changes in blood pressure. The effects of saralasin rapidly reversed after cessation of the infusion. Plasma volume was normal or high in each case. Three patients were mildly hypotensive in the control state, and all five were resistant to the pressor effect of infused AII. After three days of salt loading, the above effects of saralasin were diminished but not abolished. In four normal subjects, after salt depletion, saralasin infusion induced qualitatively similar but much smaller changes in blood pressure, PRA and PRC. In two cirrhotic patients without ascites, after salt depletion, saralasin infusion caused a rise in blood pressure with no significant changes in PRA, PRC or PA. These results provide evidence that in patients with cirrhosis and ascites circulating AII is active in support of blood pressure, in direct suppression of renal renin release, and in stimulation of aldosterone release.     

Biological activity of des-Asp1-,Ileu8-angiotensin II (Ileu8-angiotensin III) in man

Biological activity of ileu8-angiotensin III (AIIIA) was studied in man. In 5 normal men intravenous infusion of 200 ng/kg/min of AIIIA for 30 minutes from 0900 h had no effect on blood pressure (BP) but caused a decrease in plasma renin activity (PRA) and an increase in plasma aldosterone (PA). This dose did not inhibit pressor and steroidogenic actions of angiotensin II (AII) infused into the normal men at a rate of 20 ng/kg/min for 30 minutes. In 3 patients with Bartter's syndrome 260-1,200 ng/kg/ min of AIIIA infusion for 30 minutes from 0900 h had no effect on BP but caused decreases in PRA and PA. These results indicate that in man AIIIA has no pressor action and no antagonistic effect on pressor action of AII but has PRA-lowering and aldosterone-stimulating effects. Antagonistic effect of AIIIA on steroidogenic action of AII was also shown in patients with Bartter's syndrome but not in AII-treated normal men. This may be due to the difference of administered dose of AIIIA.     

Renin, aldosterone and arterial pressure responses to acute beta-adrenergic receptor blockage in hypertensive patients

The effect of acute (intravenous) beta-adrenergic blockade with propranolol or pindolol on arterial pressure (BP), plasma renin activity (PRA), and plasma concentration of aldosterone (PA) was evaluated in 20 essential hypertensive men. BP, PRA and PA were determined during continuous recumbency over-night (8 p.m. to 6 a.m.) every 30 min. Two groups of patients were observed. Patients of group 1 exhibited a characteristic day-night rhythm of PRA with low values before midnight and large increases early in the morning. Conversely, no rhythm and very low PRA values were observed in patients of group II. BP was higher in group II than in group I. In group I following intravenous propranolol or pindolol, BP fell within minutes and levels as well as rhythms of PRA were converted to those of group II without treatment. In group II day-night profiles of PRA and BP remained unchanged. Rhythm and concentration of PA in the two groups were not influenced by either drug. In 4 patients of group I infusion of angiotensin II inhibitor did not lower BP. The observations suggest that in the two groups dissimilarities in rhythms of PRA as well as in BP responses to beta-blockade may reflect differences in neuro-adrenergic tone.     

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.     

Effect of sodium restriction and angiotensin II infusion in Bartter's syndrome

Five patients with Bartter's syndrome were investigated. Sodium restriction (less than 10 mEq/day for at least 5 days) showed a renal sodium wastage in only two patients (I and II) in spite of increased aldosterone secretion rate (from 151-427 to 680-842 mug/day). The effect of angiotensin II (A II) 80ng/kg/min for 30-180 min, on plasma renin activity (PRA), plasma aldosterone, and urinary sodium excretion was compared with the effect of a previous infusion of 5% dextrose given at the same rate, 0.5 ml/min for 1 hr. A II infusion resulted in increased plasma aldosterone levels: from 236-330 pg/ml to 800-881 pg/ml in 30 min. This increase was also observed in patient II (from 139 to 600 pg/ml). PRA was decreased by A II infusion (from 1,142-2,462 to 121-1,625 ng/liter/min). In patient IV, this decrease in PRA was also observed when he was on a salt-restricted diet (from 1,934 to 370 ng/liter/min); but the minimal PRA was still higher (370 ng/liter/min) than with a normal diet (121 ng/liter/min). In no case could normal PRA level be obtained. A II infusion induced an increase in urinary sodium excretion only in the two patients with renal sodium wastage (from 80-90 to 265-230 muEq/min in 30 min). Urinary sodium excretion decreased in the other patients from (37.5-213 to 4.30-46 muEq/min) and fractional sodium excretion was reduced in patient V (from 0.56% to 0.45% at 30 min and to 0.29% at 120 min). No significant change with A II infusion was observed in patient IV when he was on a sodium-restricted diet (from 1 to 2.5 muEq/min in 30 min). Urinary potassium excretion was similar to sodium excretion. No change was observed in plasma potassium and sodium.     

Hypertension associated with early stage kidney disease. Complementary roles of circulating renin, the body sodium/volume state and duration of hypertension

Interrelations among blood pressure, exchangeable sodium, blood volume and plasma renin activity were studied in 40 normal subjects and in 40 patients with early stage kidney disease (mean plasma creatinine, 2 mg/100 ml). Findings in eight normotensive patients did not differ significantly from those in normal subjects. However, 32 hypertensive patients showed increases (p less than 0.05) in mean exchangeable sodium and in the products of the logarithm of plasma renin activity and exchangeable sodium or blood volume. In normal subjects, blood pressure did not correlate with any of the parameters measured. In the patients, it correlated significantly (p less than 0.05) with duration of hypertension (r = 0.70), exchangeable sodium (r = 0.34) and with sodium-renin (r = 0.38) or volume-renin (r = 0.30) products, but not with blood volume or circulating renin individually. Multiple regression analysis with blood pressure as a dependent variable, and duration of hypertension and the sodium-renin or volume-renin products as independent variables, revealed correlation coefficients of 0.77 and 0.76, respectively. These findings suggest that hypertension accompanying early stage kidney disease may depend at least partly on subtle abnormalities in the sodium volume-renin feedback mechanism as well as on a factor related to the duration of preexisting hypertension.     

Ambulatory blood pressure changes in the menstrual cycle of hypertensive women. Significance of plasma renin activity values

Blood pressure (BP) changes during the menstrual cycle (MC) have not been studied in hypertensive women in relationship to changes in sex hormone levels and plasma renin activity (PRA). We therefore carried out 24 h ambulatory BP recordings and hormonal measurements in 34 hypertensive and 27 matched normotensive women during the follicular ovulatory and luteal phases of the menstrual cycle. Plasma renin activity was similar in the two groups and rose significantly during the luteal phase only in the hypertensives (P < .01). There were no differences in plasma estradiol or progesterone between the normotensives and hypertensives, but testosterone was higher in the hypertensives during the ovulatory (P < .01) and luteal (P < .001) phases. Blood pressure did not change in the normotensives throughout the cycle, but it increased in the hypertensives during ovulation (P < .01). When patients were divided according to mean menstrual cycle PRA, only those with relatively low PRA (< 2 ng/mL/h) had a significant BP rise during ovulation and it primarily occurred at night (P < .05). The results demonstrate that premenopausal hypertensive women have increased testosterone during ovulation and increased testosterone and PRA during the luteal phase of the cycle. Like normotensives, hypertensives with relatively high PRA exhibit no change in BP during the cycle, whereas those with relatively low PRA have a nighttime increase in BP during ovulation.     

Raised plasma-prolactin levels in essential hypertension: index of reduced hypothalamic dopaminergic activity (author's transl)

Serial measurements of plasma-prolactin concentration (HPr) and plasma-renin activity (PRA) at 30-min intervals were made in 19 male patients with essential hypertension and in 8 normotensive subjects. HPr was markedly higher in the hypertensive patients than in the normotensive controls. Patients with reduced plasma-renin activity and only slightly elevated HPr-levels showed lower urinary sodium excretion, but a more pronouced 24-h natriuretic response to i.v. furosemide than patients with normal renin and very high HPr-levels. Six patients were treated with the dopaminergic agonist bromocriptine. The drug induced a significant blood pressure reduction in five patients and normalised pressure in two patients. The data do not indicate a role for prolactin in sustaining hypertension via renal salt retaining mechanisms. It is suggested that the raised HPr-levels represent an index of altered central nervous function, characterized by reduced hypothalamic activity. The blood pressure-lowering effect of the dopaminergic agonist bromocriptine fits with the hypothesis that reduced hypothalamic dopaminergic activity might be a factor in the pathogenesis of essential hypertension.     

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.     

Effect of estrogen upon the juxtaglomerular apparatus and the renin-angiotensin system in rats

Administration of 1.5 mg/kg of estriol intramuscularly and 15 mg/kg of stilbestrol disulfate intraperitoneally daily for 15 days caused an increase in plasma renin substrate (PRS), accompanied by an increase in plasma renin activity (PRA) and a slight decrease in plasma renin concentration (PRC). Contrary to the slight suppression of PRC, juxtaglomerular granulation index (JGI) was significantly increased in rats treated by estrogen. In the rats which developed hypertension by estrogen PRA, PRC and JGI were a little higher than those in the rats which remained normotensive after the same estrogon treatment, but these differences were not statistically significant. Therefore, it seems rather difficult to attribute the development of estrogen hypertension only to the quantitative changes in the renin-angiotensin system.     

Effect of bucladesine sodium on the plasma concentrations and urinary excretion of purine bases and uridine

To examine whether bucladesine sodium affects the plasma concentrations of purine bases (hypoxanthine, xanthine, and uric acid) and uridine, 100 mL of physiological saline containing bucladesine sodium (6 mg/kg weight) was administered intravenously to eight healthy subjects for 1 hour after overnight fast except for water. Blood was drawn 30 minutes before, and 30 minutes and 1 hour after the beginning of the infusion, and 1-hour urine was collected before and after the beginning of the infusion. Two weeks later, 100 mL of only physiological saline was administered under the same protocol. Bucladesine sodium decreased the plasma concentrations of hypoxanthine by 36% and by 37%, and of xanthine by 16% and 33%, and of uridine by 17% and 30%, 30 minutes and 1 hour after the beginning of the infusion, respectively, and increased the urinary excretion of hypoxanthine and uric acid by 140% and 30%, respectively, after the beginning of the infusion. However, it did not affect the plasma concentration of uric acid or the urinary excretion of xanthine, and the urinary excretion of uridine was less than 0.2 micromol/h before or after bucladesine sodium infusion. On the other hand, physiological saline alone did not affect any of the values described. These results suggest that bucladesine sodium acts on the secretory process of the renal transport of hypoxanthine, resulting in the increased urinary excretion of hypoxanthine, and further suggest that bucladesine sodium enhances the uptake of uridine in plasma to liver cells.     

Hypertension treatable with glucocorticoids: report of a case

Lately, a series of hypertensive syndromes of unknown etiology that respond to new forms of therapy, have been described. One of these is glucocorticoid remediable hypertension, that evolves with suppressed plasma renin activity and normal or high serum aldosterone levels, that lead to an aldosterone/plasma renin activity ratio over 30. We report a 45 years old woman with a severe hypertension, despite the use of antihypertensive medications. She had a plasma renin activity of less than 0.3 ng/ml/h, normal serum aldosterone levels (10 ng/ml) and thus a high aldosterone/plasma renin activity ratio. She had normal serum potassium and sodium levels. Due to the bad results of conventional antihypertensive medications, a treatment with dexamethasone was started, that normalized blood pressure and allowed to discontinue other antihypertensive medications. This type of hypertension must be sought since non conventional treatments could be used for refractory hypertensive syndromes.     

Lipolytic sensitivity and response to fasting in normotensive and hypertensive obese humans

Obese persons with hypertension are at greater risk for diabetes and hyperlipidemia than normotensive obese persons. It has been postulated that increased lipolytic rates contribute to these metabolic diseases. Therefore, we evaluated the glycerol rate of appearance (Ra) in plasma, an index of whole-body lipolytic activity, during basal conditions and during 60 minutes of epinephrine infusion after 12 and 84 hours of fasting in six normotensive (body mass index [BMI], 39.9 +/- 1.8 kg/m2) and six hypertensive (BMI, 38.7 +/- 1.6 kg/m2) obese persons. Basal glycerol Ra was lower in hypertensive than in normotensive subjects at both 12 hours (1.58 +/- 0.21 v 2.27 +/- 0.28 mumol/kg/min, respectively; P < .01) and 84 hours (2.04 +/- 0.06 v 2.50 +/- 0.13 mumol/kg/min, respectively; P < .01) of fasting. Peak glycerol Ra during epinephrine infusion after 84 hours of fasting (5.69 +/- 0.72 and 11.40 +/- 0.78 mumol/kg/min for hypertensive and normotensive subjects, respectively) was significantly greater than at 12 hours (3.09 +/- 0.29 and 5.06 +/- 0.69 mumol/kg/min) in both hypertensive and normotensive subjects. However, peak glycerol Ra was lower in hypertensive than in normotensive subjects after 12 and 84 hours of fasting (P < .01 for 84 hours). We conclude that hypertension in obese persons is associated with a decrease in both basal lipolytic rates and lipolytic sensitivity to epinephrine infusion.     

Circulating plasma prekallikrein and tissue kallikrein in normotensive and hypertensive humans: effects of angiotensin II infusion

Kinins lower blood pressure but the stimuli leading to kinin generation and their origin are less well known. We administered angiotensin II in graded infusion doses to patients with primary hypertension and normotensive controls to study the effects of on circulating kallikreins. Angiotensin II infusion did not significantly alter plasma prekallikrein or tissue kallikrein levels and the plasma levels and their changes did not correlate with blood pressure levels or changes. In the normotensive group prekallikrein levels and renin activity correlated negatively with urinary sodium and chloride excretion during basal conditions and partially during the infusion. U-tissue kallikrein concentration increased in the normotensive group. Thus, acute elevation of blood pressure induced by angiotensin II does not activate the circulating kallikrein-kinin systems. Data rather indicate that the circulating kallikrein-kinin systems may be related to alterations in volume and sodium balance and that these mechanisms may be altered in primary hypertension.     

Intralymphocyte free magnesium in a group of subjects with essential hypertension

Despite the importance of magnesium in essential hypertension, few data are available on the ionized intracellular concentration of this ion. We therefore studied intralymphocyte free intracellular magnesium (Mgi) in 32 untreated essential hypertensive subjects and 27 normotensive control subjects by means of a fluorimetric technique based on the use of the new magnesium-sensitive dye furaptra. We also measured intralymphocyte ionized calcium (Cai) with fura 2. No statistically significant differences were found in Mgi in hypertensive compared with normotensive subjects (essential hypertensive, 0.291 +/- 0.053 mmol/L; normotensive, 0.293 +/- 0.043 [mean +/- SD]). A statistically significant inverse correlation was established between Mgi and plasma triglycerides in essential hypertensive subjects (r = -.521, P = .002). The hypertensive group was arbitrarily divided into two subgroups according to plasma triglyceride levels (> 2 [n = 10] or < 2 mmol/L [n = 22]), and Mgi proved to be significantly lower in the subgroup with high plasma triglyceride levels compared with either the subgroup with normal triglycerides (P = .009; 95% confidence interval, 0.013-0.088) or the normotensive control group as a whole (P = .03; 95% confidence interval, 0.003-0.069) (high-triglyceride hypertensive subgroup, Mgi = 0.256 +/- 0.045 mmol/L; normal-triglyceride hypertensive subgroup, Mgi = 0.307 +/- 0.049). No statistically significant differences were found in Cai in hypertensive compared with normotensive subjects (hypertensive, 53 +/- 12 nmol/L; normotensive, 54 +/- 14). We did not find statistically significant correlations between Cai and plasma triglycerides, nor did we find any differences in Cai between the subgroup of hypertensive subjects with high plasma triglyceride levels and either the subgroup of hypertensive subjects with normal triglycerides or the normotensive control group as a whole. The discrepancies between our results in lymphocytes and data relating to either erythrocytes or platelets emphasize the need for caution before the results are extrapolated from one tissue to the other. The decreased Mgi levels in the subgroup of high-triglyceride hypertensive subjects may suggest a role for magnesium in plurimetabolic syndrome.     

Neutral endopeptidase inhibition potentiates the effects of natriuretic peptides in renin transgenic rats

The influence of neutral endopeptidase (NEP) inhibition with (S)-thiorphan on the hormonal, renal, and blood-pressure-lowering effects of an infusion of atrial (ANP), brain (BNP), and C-type natriuretic peptide (CNP) was evaluated in hypertensive transgenic rats (TGR) harboring an additional mouse renin gene (TGR(m(Ren2)27)). These TGR possess an activated natriuretic peptide system as compared with Sprague-Dawley rats (SDR), used in this study as control. (S)-Thiorphan significantly decreased blood pressure in anesthetized TGR but not in anesthetized SDR during the 60-min infusion period. Exogenously administered ANP decreased blood pressure in SDR with no significant effects in TGR after 60 min. In contrast, BNP infusion significantly decreased blood pressure in TGR, while changes in SDR were not significant. The blood pressure was further decreased after combined infusion of ANP and BNP with (S)-thiorphan in TGR. No effect on blood pressure was registered during infusion of CNP in either experimental group. The plasma levels of ANP, BNP, and cGMP were higher in TGR than in SDR, whereas plasma renin activity was lower. Co-administration of ANP, BNP, or CNP with the NEP inhibitor (S)-thiorphan potentiated the plasma ANP, BNP, and cGMP. Infusion of ANP alone did not affect BNP plasma levels of TGR and vice versa. In contrast, CNP infusion increased ANP plasma levels in both TGR and SDR. Renal excretion of sodium and cGMP increased after infusion of (S)-thiorphan and ANP or BNP in both TGR and SDR. The combination of ANP and (S)-thiorphan had a slightly greater effect on urinary excretion of sodium and cGMP in TGR than either compound alone, but the effects were more pronounced in SDR than in TGR. Finally, infusion of CNP alone and in combination with (S)-thiorphan influenced the excretion of sodium and cyclic GMP only slightly. These results indicate that inhibition of neutral endopeptidase by (S)-thiorphan potentiates the hemodynamic and renal effects of natriuretic peptides ANP and BNP, and to some extent those of CNP, in hypertensive TGR and normotensive SDR. In contrast to ANP and BNP, infusion of CNP had no effect on the blood pressure in anesthetized TGR or SDR. Inhibition of NEP therefore seems to be a promising way to potentiate endogenous levels of natriuretic peptides, which may be of therapeutic benefit in cardiovascular diseases such as hypertension or heart failure.     

Renal trauma and hypertension: the role of renin

Three patients developed hypertension following renal trauma. Trauma produced perinephric hematoma in two and renal artery thrombosis in one. Renal vein plasma renin activity (PRA) from the traumatized kidney was three to eight times greater than renal vein PRA from the untraumatized (contralateral) kidney. Peripheral PRA was elevated in all. A surgical operation lowered peripheral PRA to normal in all, but corrected hypertension in only two of three. Preoperative medical treatment with renin-suppressing pharmacologic agents correctly predicted this response to surgery. Postoperative renal vein PRA in the remaining hypertensive patient demonstrated that surgery successfully alleviated the abnormality in renin secretion. These studies suggest that excessive renin secretion initiate but other unidentified factors may contribute to the hypertension observed after renal trauma.