Changes In Plasma Renin Activity Research Articles

Natriuresis and blood pressure in patients with chronic renal failure following L-arginine infusion

Nitric oxide (NO) is known to be generated from L-arginine and may regulate glomerular filtration, tubular sodium reabsorption, and renin secretion. Impairment of renal function might influence NO production secondary to endothelial dysfunction, decreased NO synthesis and increased activity of arginine analogues inhibiting NO synthase. In this study, we evaluated the effect of L-arginine on the blood pressure and urinary sodium excretion in patients with chronic renal failure. A 300-ml dose of 10% L-arginine solution was administered intravenously over 30 min and blood pressure was monitored every 10 min under basal conditions and for 120 min after infusion. The patients were divided into two groups based on the reduction in mean blood pressure (dMBP) following infusion, namely non-responders (dMBP < 10 mmHg) and responders (dMBP > 10 mmHg). Urine and blood samples were collected to determine electrolytes, urinary NO2 + NO3 by the Griess method, urinary cGMP, plasma renin activity (PRA), and the plasma aldosterone concentration (PAC). L-arginine significantly decreased MBP in 8 patients and caused no significant change in 10 patients. Urinary sodium excretion and the NO2 + NO3 level were significantly increased following L-arginine infusion and the increment of fractional excretion of sodium was higher in responders. However, there were no significant changes in PRA, PAC, and cGMP. Our findings suggest that a vasodilator effect of NO induced by L-arginine loading may, at least in part, be associated with increased renal sodium excretion in patients with chronic renal failure.

Effects of Propranolol on Cardiovascular and Neurohumoral Actions of Alcohol in Hypertensive Patients

Alcohol ingestion acutely lowers blood pressure (BP) with vasodilation and sympathetic activation in Oriental subjects. We examined the effects of beta blockade on cardiovascular and neurohumoral actions of alcohol in Japanese men with mild-to-moderate essential hypertension. Ten hypertensive patients (54+/-5 years, mean+/-SE) were given 1 ml/kg of alcohol or isocaloric control drink with a light meal in the evening before and 5-7 days after treatment with propranolol (20 mg three times daily). BP and heart rate (HR) were measured every 30 min for 24 h in each period. Blood sampling and echocardiographic examination were carried out before (17.00 h) and after (19.00 h) intake of alcohol or control drink, Before treatment, alcohol ingestion caused significant decreases in BP, total peripheral resistance and serum potassium concentration, while it increased heart rate (HR), cardiac output (CO), plasma norepinephrine and plasma renin activity (PRA). Treatment with propranolol significantly decreased BP and HR for 24 h. Propranolol and alcohol showed an additive depressor effect on night-time BP, and the alcohol-induced hypotension was similar before and after propranolol treatment. The alcohol-induced changes in HR, CO, PRA and serum potassium were significantly attenuated by propranolol. These results suggest that activation of the sympathetic nervous system plays a role in alcohol-induced cardiac stimulation, renin release and hypokalemia through beta receptors. Moderate doses of beta-blockers may not modify alcohol-induced BP reduction in Oriental subjects with hypertension.

EFFECT OF REPEATED ADMINISTRATION OF CADMIUM, CAPTOPRIL AND ITS COMBINATION ON PLASMA RENIN ACTIVITY IN RATS

The effects of normal saline (1 ml kg−1, i.p. for 5 days), cadmium acetate (1 mg kg−1, i.p. for 5 days), captopril (20 mg kg−1, p.o. for 5 days), or captopril (20 mg kg−1, p.o. for 5 days) plus cadmium acetate (1 mg kg−1, i.p. for 5 days) on blood pressure (BP), heart rate (HR), plasma renin activity (PRA) and respiratory rate (RR) were examined in male Sprague–Dawley (S–D) rats. Repeated administration of cadimum acetate produced a hypertensive response (P<0.01) without significant changes in PRA, HR or RR. The captopril group was associated with hypotension (P<0.01) but again PRA, HR and RR were not significantly altered. In the group receiving captopril p.o. and cadmium i.p., BP rose significantly compared with captopril alone but PRA, HR, RR were not altered. Cadmium-induced hypertension cannot be obviously accounted for on its basis of augmented plasma or tissue renin angiotensin involvement

Catecholamine and renin-angiotensin response during controlled hypotension induced by prostaglandin E 1 combined with hemodilution during isoflurane anesthesia

Study Objective: To evaluate the catecholamine and renin-angiotensin response during controlled hypotension combined with hemodilution in the clinical setting. Design: Randomized, prospective study. Setting: Inpatient surgery at Nagasaki Rosai Hospital. Patients: 30 ASA physical status I and II female patients scheduled for total hip arthroplasty. Interventions: Patients were randomly divided into three groups. Group A (N = 10) received hemodilution alone. Group B (N = 10) received controlled hypotension alone. Group C (N = 10) received hemodilution plus controlled hypotension. Hemodilution was carried out after induction of anesthesia, in which drawn blood was replaced with 6 % hydroxyethyl starch, and the final hematocrit value was approximately 22%. Controlled hypotension was induced with prostaglandin E 1 (PGE 1) to maintain mean arterial blood pressure at 55 mmHg for 80 minutes. Measurements and Main Results: Measurements included plasma renin activity (RA) and plasma concentrations of angiotensin-II (AG-II), aldosterone (AS), norepinephrine (NE), and epinephrine (EP). These indices were measured before hemodilution, after hemodilution, 80 minutes after starting hypotension, and 60 minutes after recovery from hypotension. Hemodilution alone caused no significant change in the values throughout the time course. Controlled hypotension alone caused significant increases in plasma concentrations of NE (+295%) and EP (+203%) at 80 minutes after starting hypotension, whereas it caused no change in plasma RA and plasma concentrations of AG-II and AS. Hemodilution plus controlled hypotension caused significant increases in plasma RA(+271%) and plasma concentrations of AG-II (+188%), AS (+199%), NE (+279%), and EP (+184%) at 80 minutes after starting hypotension. Conclusion: The combination of hemodilution and PGE 1 induced controlled hypotension causes significant responses, especially in a renin-angiotensin-aldosterone system under isoflurane anesthesia.

AT1 and TxA2/PGH2 receptors maintain hypertension throughout 2K,1C Goldblatt hypertension in the rat.

Angiotension II (ANG II) increases the generation of vasoconstrictor prostaglandin endoperoxides (PGH2) and thromboxane A2 (TxA2). Two-kidney, one-clip (2K,1C) Goldblatt hypertensive rats have an increased plasma renin activity (PRA) and ANG II level during the early, but not the late, phases of hypertension. Therefore, the aim of these studies was to compare the antihypertensive efficacy of an ANG II type I (AT1) and a TxA2/PGH2 receptor antagonist during different phases of 2K,1C hypertension. Rats were maintained on a fixed sodium intake for 3 days before and throughout the period of drug administration. These studies assessed the antihypertensive response to administration of the AT1 receptor antagonist losartan (20 mg.kg-1.day-1), the TxA2/PGH2 receptor antagonist ifetroban (20 mg.kg-1.day-1) or vehicle given for 3 days to rats with early (2-4 wk postclip), intermediate (10-12 wk postclip), and late (36-42 wk post-clip) 2K,1C hypertension and to two control groups of rats corresponding in age to the early or intermediate and the late 2K,1C groups. The mean arterial pressure (MAP) was measured directly with indwelling arterial cannulas. The MAP of sham-operated rats was 109 +/- 5 mmHg. In the early phase of 2K,1C hypertension, the MAP was increased to 143 +/- 6 mmHg, and it was increased further to 162 +/- 5 mmHg during the intermediate and to 179 +/- 4 mmHg during the late phase. The PRA, compared with age-matched controls, was increased during early and intermediate, but not late phase 2K,1C hypertension. Neither drug lowered blood pressure in control rats. However, both drugs significantly reduced the blood pressure in the early, intermediate, and late phases of 2K, 1C hypertension. At the end of 3 days of administration, blood pressure in early 2K, 1C rats given losartan was reduced to levels of control rats, but remained slightly elevated in other groups and in those receiving ifetroban. In conclusion, AT1 and TxA2/PGH2 receptors maintain hypertension throughout the evolution of 2K, 1C hypertension in the rat, despite changes in PRA.

Blockade of nitric oxide formation inhibits the stimulation of the renin system by a low salt intake

This study aimed to investigate the possible involvement of endothelial autacoids such as nitric oxide or prostaglandins in the well-known stimulatory effect of a low salt intake on renin secretion and renin gene expression in the kidney. To this end, plasma renin activity (PRA) and kidney renin mRNA levels were determined in male Sprague-Dawley rats fed either a normal (0.6% w/w) or a low (0.03%) NaCl diet for 10 days. To inhibit nitric oxide formation, the animals received L-nitro-argininemethylester (L-NAME, 40 mg/ kg twice a day), to inhibit prostaglandin formation the animals received meclofenamate (8 mg/kg twice a day) during the last 2 days. In animals fed a normal salt diet, L-NAME decreased PRA from 6.5 to 4.9 ng angiotensin I x h(-1) x ml(-1) and decreased renin mRNA levels by about 15%. Meclofenamate did not change PRA or renin mRNA in animals fed on normal salt diet. In vehicle-treated animals fed a low salt diet, PRA increased from 6.5 to 20.2 ng ANGI x h(-1) x ml(-1) and renin mRNA levels increased by 100%. Meclofenamate treatment did not alter these changes of PRA and renin mRNA during the intake of a low salt diet. In animals treated with L-NAME, PRA increased to only 7.2 ng ANGI x h(-1) x ml(-1) and renin mRNA increased by 20%. These findings indicate that inhibition of nitric oxide formation but not of prostaglandin formation substantially attenuates the stimulatory effect of a low salt intake on the renin system, suggesting that nitric oxide is required for this process.

Acute hemodynamic effects of ciprokiren, a novel renin inhibitor, in sodium-depleted dogs.

We evaluated the acute hemodynamic effects of ciprokiren (Ro 44-9375), a new potent renin inhibitor, in sodium-depleted dogs. After dogs were sodium depleted by administration of furosemide, they were anesthetized, and effects of increasing doses of ciprokiren (0.1-3 mg/kg) or placebo on arterial blood pressure (BP), cardiac output (CO), coronary blood flow (CBF), left ventricular (LV) + dP/dtmax, and plasma renin activity (PRA) were evaluated. Ciprokiren dose-dependently decreased arterial BP and peripheral vascular resistance (PVR), beginning at the 0.1-mg/kg dose and having maximal effect at 1 mg/kg. Ciprokiren did not change heart rate (HR), LV + dP/dtmax or coronary vascular resistance. Finally, a maximal effective dose of an angiotensin-converting enzyme (ACE) inhibitor (cilazapril 1.0 mg/kg intravenously, i.v.) had no additional hemodynamic effect. At 0.1 mg/kg ciprokiren, arterial BP was reduced, with no change in PRA, showing the dissociation between hemodynamic effects and inhibition of renin in plasma. Acutely, renin inhibition with ciprokiren produces a marked peripheral vasodilation which appears to be dissociated from the renin inhibition in plasma and which is not increased by additional ACE inhibition.

The Role of Adenosine in Promoting Cardiac -Adrenergic Subsensitivity in Aging Humans

The mechanism by which aging decreases the cardiac chronotropic response in human subjects is unknown. We investigated the role of endogenous adenosine in attenuating the chronotropic response to beta-adrenoceptor stimulation due to aging by employing the adenosine receptor antagonist, theophylline. Sixteen healthy elderly (67.1 +/- 1.3 yrs) and sixteen healthy young (26.1 +/- 0.6 yrs) subjects were studied. The bolus dose of isoproterenol necessary to increase the heart rate 25 beats per minute (I25) was determined by calculating the log dose response curve before and after a 30-min infusion of theophylline (6.5 mg/kg) in each subject. In addition, the effect of theophylline on the orthostatic increase in plasma renin activity (PRA) was determined. The I25 for the elderly and young groups were 34.55 +/- 6.98 and 10.85 +/- 1.93 ng/kg, respectively (p < .01). After theophylline administration, the difference in I25 in the two groups was no longer present (13.32 +/- 2.72 vs 7.46 +/- 1.26 ng/kg). The dose ratios (I25 after theophylline/I25 before theophylline) in the elderly and young groups were 0.43 +/- 0.06 and 0.82 +/- 0.14, respectively (p < .05). After the administration of theophylline, the orthostatic increase in PRA was enhanced more in the elderly subjects (0.53 +/- 0.23 vs 1.54 +/- 0.35 ng AI/ml/hr; p < .01) than in the young (1.31 +/- 0.23 vs 2.49 +/- 0.53 ng AI/ml/hr; p-value n.s.). Plasma norepinephrine changes after theophylline and postural norepinephrine changes after theophylline were not different in the two age groups. Excessive adenosine production or effect is partly responsible for the cardiac chronotropic resistance to isoproterenol and the diminished postural change in PRA in the elderly.

948-52 Paradoxical Neurohumoral Axis Inhibition After Body Fluid Volume Depletion in Patients with Congestive Heart Failure and Water Retention

Hypovolemia stimulates the sympathoadrenal and renin systems and water retention. In congestive heart failure (CHF) reduction of cardiac output (CO) and, to the extent that it occurs, decrease of blood pressure (BP), have been suggested to be perceived as a state of underfilling of the arterial compartment, and to promote and perpetuate neurohumoral activation and retention of fluid. This study was aimed to probe whether intravascular volume deficit accounts for patterns that largely exceed the limits of a homeostatic response, as sometimes observed in more advanced stages of the syndrome. We reduced the body fluid mass with a non-pharmacological method, ultrafiltration (UF), in patients with CHF and water retention, and monitored the neurohumoral reaction. In 22 patients, UF was performed with a diafilter, which was part of an external venous circuit, whose flow was regulated to produce 500 ml/hour of ultrafiltrate (average total amount = 3122 ± 1199 ml) until right atrial pressure was lowered to 50% of baseline. Hemodynamics, plasma renin activity (PRA), norepinephrine (NE) and aldosterone (AL) were evaluated before and in the 48 hours after UF. Soon after the procedure, associated with a 20% reduction of plasma volume (PV) and a moderate decrease of CO and BP (consistent with a diminished degree of filling of the arterial compartment), there was an obvious fall of NE, PRA and AL. In the next 48 hours we recorded a) recovery of PV. CO and BP, b) increasing depression of the neurohumoral axis, c) striking enhancement of water and sodium excretion and resolution of peripheral edema and organ congestion. Changes of NE, PRA or AL were not related to changes of PV. CO and BP (variations in the state of arterial filling) and significantly correlated with the increase of urinary output and sodium excretion. Arterial underlilling, as a the main mechanism for activation of the neurohumoral axis and retention of fluid, does not apply to the more advanced stages of CHF. The parallelism observed between fall of circulating hormones and reabsorption of extravascular fluid suggests that hypoperfusion and/or congestion of organ, like kidney and lung, may reduce the clearance of circulating norepinephrine and contribute to keep renin and aldosterone raised. A positive feedback loop between fluid retention and plasma hormone levels appears to be a mechanism of progression of the syndrome.

Reciprocal changes in vasoactive hormones in the rat myocardial infarction model of heart failure

The purpose of this study was to determine (1) if there is a relationship between the changes in the plasma levels of atrial natriuretic peptide (ANP) and plasma renin activity (PRA) as rats compensated from 3 days to 6 weeks after coronary ligation and (2) if these changes are related to myocardial infarction (MI) size. Arterial blood was drawn twice from 34 conscious rats (control, n = 10; small MI, n = 10; large MI, n = 14). Histologic MI size correlated better with ANP 3 days ( r = .72, P < .001) than with ANP 6 weeks after MI ( r = .39, P = .021). The reverse was true for an electrocardiographic index of MI size that used the sum of the Q waves minus the sum of the R waves in leads I, aVL, and V 5. Atrial natriuretic peptide at 3 days was increased in both MI groups and was highest in the large MI group (control, 25.6; small MI, 41.0; large MI, 58.6 pM). Atrial natriuretic peptide decreased significantly from 3 days to 6 weeks in the large MI group and normalized in the small MI group (control, 25.0; small MI, 26.4; large MI, 44.4 pM). Plasma renin activity was not elevated at either time. However, the change in ANP from 3 days to 6 weeks in the MI rats was negatively related to the change in PRA ( r = .48, P = .016). Atrial natriuretic peptide levels early after MI may be a good predictor of infarct size. The pattern of ANP and PRA changing in opposite directions over time suggest a counterregulatory link between these two systems.

Sleep-associated variations in plasma renin activity and blood pressure in the rat

Plasma renin activity (PRA) was determined in plasma samples obtained approximately at 6-min intervals during consecutive non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) periods in rats chronically implanted with EEG electrodes, a brain thermistor, and an intracardiac catheter. PRA was low in REMS and high in NREMS; this difference was statistically significant. The PRAs in wakefulness and NREMS were not different. Sleep-associated variations in systemic blood pressure (BP) were also recorded in a group of rats implanted with a chronic aortic catheter. During REMS, large oscillations superimposed on a tonic rise in BP were observed, and the end of REMS was followed by an abrupt fall in BP. This is the first demonstration of sleep-associated variations in PRA in a species other than man. The changes in BP in the rat during REMS confirm previous reports and, unlike those in many other species, are similar to those previously described in humans. The rat therefore provides a model for study of the mechanisms of the sleep-related variations in PRA and BP. The changes in PRA may reflect a regulatory response to variations in BP or may result from central mechanisms, e.g. the sleep-associated changes in serotonergic activity.

Association of a nocturnal rise in plasma alpha-atrial natriuretic peptide and reversed diurnal blood pressure rhythm in hospitalized normotensive subjects with non-insulin dependent diabetes mellitus.

Diurnal changes in plasma atrial natriuretic peptide (ANP), plasma renin activity (PRA) and plasma aldosterone as related to those in blood pressure (BP) were studied under hospital conditions in 18 diabetic subjects without proteinuria and 8 age-matched control subjects. Of 18 diabetic subjects, 10 had a normal diurnal BP rhythm with the peak value in the afternoon (group 1) and 8 had a reversed BP rhythm with the peak value during the night (group 2). Autonomic dysfunction estimated by measuring orthostatic BP and heart-rate changes and beat-to-beat heart-rate variations was more pronounced in group 2 than in group 1. Fasting plasma glucose and HbA1c were similarly high in both diabetic groups. Group 1 showed modestly elevated mean 24-h MBP and plasma ANP levels, modestly low mean 24-h PRA and plasma aldosterone levels, and a lack of diurnal ANP changes similar to that in controls. Group 2 showed markedly elevated mean 24-h BP and plasma ANP levels, markedly low mean 24-h PRA and plasma aldosterone levels, and nocturnal rises in plasma ANP and BP. PRA and plasma aldosterone exhibited circadian rhythms with their peak values found in the early morning in all three groups. The daytime/overnight excretion ratios of sodium and water were normal in group 1 and low in group 2. These results indicate that diurnal changes in plasma ANP, PRA and plasma aldosterone are altered in diabetic subjects with normal and reversed diurnal BP rhythms, predominantly in the latter.

Simultaneous measurement of plasma 18-oxocortisol and 18-hydroxycortisol levels in normal man.

Plasma 18-oxocortisol (18-oxoF) and 18-hydroxycortisol (18-OH-F) were measured in 47 healthy subjects. Plasma 18-oxoF and 18-OH-F in the early morning were 0.827 +/- 0.04 nmol/l and 3.29 +/- 0.175 nmol/l, respectively. The plasma levels of both steroids correlated with each other and with cortisol, but not with aldosterone. Postural stimulation with or without furosemide administration increased 18-oxoF, 18-OH-F, aldosterone and plasma renin activity (PRA). Two hours after 2 mg of oral dexamethasone administration or after an overnight 2 mg of dexamethasone suppression cortisol, 18-oxoF and 18-OH-F decreased. Cortisol, aldosterone, 18-oxo-F and 18-OH-F increased after the intravenous administration of 250 micrograms of 1-24 ACTH. Changes in plasma 18-oxo-F and 18-OH-F levels correlated with PRA change during the posture studies and correlated with the change of ACTH during the dexamethasone studies. The ratios of post-/pre-test values of the postural stimulation and dexamethasone suppression in 18-oxoF and 18-OH-F were lower than that of aldosterone. Plasma 18-oxoF and 18-OH-F are more dependent on ACTH than on the renin-angiotensin system. The ratio of 18-OH-F/18-oxoF, which is between 4 and 5, remains constant during the various stimulation or suppression maneuvers.

Plasma renin activity and changes in tissue angiotensin converting enzyme

Recent evidence suggests that tissue generation of angiotensins I and II depends on the level of the plasma components of the renin-angiotensin system and on tissue-specific processes. The present study was undertaken to clarify the possible relationship between plasma renin activity (PRA) and tissue angiotensin converting enzyme (ACE) activity in the heart, lung, kidney cortex and kidney medulla of Wistar-Kyoto rats. In the kidney cortex particular attention was focused on renal brush-border ACE. Different experimental models known to have opposite effects on PRA were used: changes in salt intake, deoxycorticosterone acetate (DOCA) with or without salt supplements, and the Goldblatt two-kidney, one clip (2-K,1C) model. Two weeks after the start of the experiments the rats were killed, and PRA, and plasma and tissue ACE activity, were measured. At the end of the study the blood pressure in the treated rats was not significantly different from control. As expected, the PRA were highest in the 2-K,1C and depleted-salt groups and lowest in the DOCA, DOCA-salt and high-salt groups. ACE responses were different in different types of tissue, with no relationship between PRA and plasma or tissue ACE activity. For example, DOCA treatment led to increased ACE activity in the heart and the kidney only if the rats were maintained on a high salt intake. DOCA or salt alone failed to have this effect. In the 2-K,1C model the unclipped kidneys did not show any significant variation in ACE activity, but the clipped kidneys exhibited increased ACE activity compared with sham-operated rats. This increase, coupled with increased renal renin secretion, could play a role in the acceleration of local angiotensin II formation, and could thus initiate and sustain the development of hypertension in this model. The present results show that variations in ACE activity were organ-specific and were not linked either to hypertension or to changes in PRA.

Salt-regulating hormones in young normotensive obese subjects. Effects of saline load.

To investigate whether the response of salt-regulating hormones to volume expansion is impaired in obese subjects, we assessed the effects of saline load (0.25 mL/kg.min.120 min) in 9 young, healthy, normotensive obese subjects (body mass index, > 30 kg/m2) and in 10 lean control subjects (body mass index, < 25 kg/m2) matched for age, gender, height, and mean blood pressure. Hematocrit, plasma renin activity (PRA), plasma aldosterone (PA), atrial natriuretic factor (ANF), and urinary sodium excretion (UNaV) were evaluated. Saline load increased ANF levels significantly (P < .001) in lean subjects at both 60 and 120 minutes, whereas they decreased in obese subjects. Such decreases became significant (P < .01) at 120 minutes. Suppression of PRA and PA by saline load were more marked in lean than obese subjects. Hematocrit decreased in both groups, and UNaV increased more in lean than obese subjects during saline load. Comparisons of percent changes in ANF, PRA, and PA after saline load showed that the responses of lean and obese subjects were significantly different (P < .001 for ANF at both 60 and 120 minutes; P < .05 for PRA and PA at both 60 and 120 minutes). In conclusion, the lack of ANF response and the reduced suppression of PRA and PA to saline load indicate a dysfunction of these systems in obese subjects. This alteration may be involved in the higher susceptibility of obese subjects to developing hypertension.

Endogenouw Erythropoietin Levels in patients with Obesity-Related Hypertension.

The coincidence of increased red blood cell mass with obesity and hypertension has been confirmed in a number of studies. Since erythropoietin (EPO) induces hypertonic effect, we aimed to study the possible involvement of endogenous EPO in the pathogenesis of obesity-related hypertension (ORH). Seventy-two non-obese (body mass index-BMI 30kg/m2) patients with essential hypertension, and 32 non-obese normotensive control subjects were studied on 120mmol Na/24h diets for 3 days and 30mmol Na/24h diets for the following 3 days. Serum EPO levels, plasma renin activity (PRA), aldosterone (PAC) and urinary sodium and potassium excretion were estimated under both conditions. Hematocrit, hemoglobin and serum iron, ferritin and TIBC were measured in basal conditions. Patients with ORH showed significantly higher hematocrit values, hemoglobin levels and erythrocyte counts (p<0.05) than non-obese essential hypertensives and controls, although no differences in serum EPO levels (13.6±1.1 and 12.8±1.0mU/ml, 15.3±1.2 and 13.3±1.1, 12.2±2.0 and 10.95±1.7, respectively) and log EPO×%Hct product were found between groups. In both hypertensive groups, BMI but not blood pressure positively correlated with hematocrit. A negative correlation between changes in EPO and PRA induced by sodium restriction was found in lean hypertensive subjects only (r =-0.42, p<0.01). This finding suggests that in contrast to non-obese patients with essential hypertension, in subjects with ORH activity of the renin-angiotensin-aldosterone system does not seem to be related to EPO secretion. Since in both lean and obese essential hypertensive subjects EPO and log EPO ×%Hct product are within normal range, the contribution of endogenous EPO to the pathogenesis of hypertension in these patients is unlikely. (Hypertens Res 1994; 17: 43-48)

Influence of dietary NaCl intake on renin gene expression in the kidneys and adrenal glands of rats.

The aim of this study was to examine the influence of dietary NaCl intake on renin gene expression in the kidneys and adrenal glands of adult rats. Rats were kept on low (0.02%, w/w), normal (0.6%) or high (4%) NaCl diets and plasma renin activity (PRA) and the relative abundance of renin messenger ribonucleic acid (mRNA) in renal and adrenal tissue were followed for 20 days. In animals on a normal-salt diet PRA and renal renin mRNA levels did not change with time. PRA values in animals on the low-salt diet increased transiently (about threefold) and then declined again during the third week of treatment. Renal renin mRNA levels in these animals paralleled the changes of PRA. Conversely, in the animals kept on a high-salt diet PRA values decreased transiently and renal renin mRNA decreased continuously to about 50% of control values. Arterial blood pressure measured in conscious animals was not significantly influenced by the different salt diets. To establish whether the changes in renin mRNA levels are mediated by renal nerve input, animals on the different diets were also studied after unilateral renal denervation. Renal nerve section led to a 50% decrease of renin mRNA levels in the denervated kidneys in animals kept on the normal-salt diet. In the animals on the low-salt diet renin mRNA rose to similar levels in the denervated to those in the innervated kidney, while in animals receiving a high-salt diet renin mRNA was further decreased in the denervated kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of altitude acclimatization on fluid regulatory hormone response to submaximal exercise.

To determine the effect of altitude acclimatization on plasma levels of atrial natriuretic peptide (ANP) during submaximal exercise and its relationship with renin and aldosterone, seven male volunteers aged 17-23 yr exercised to exhaustion on a cycle ergometer at 80-85% of their maximum O2 uptake at sea level (SL; 50 m), during 1 h in a hypobaric chamber [acute altitude (AA); 4,300 m], and after 14 or 16 days of residence on the summit of Pikes Peak, CO [chronic altitude (CA); 4,300 m]. Plasma samples taken before exercise, 10 min after the start of exercise, and 5 min postexercise were analyzed for ANP, plasma renin activity (PRA), and aldosterone (ALDO). ANP showed a progressive increase from rest to postexercise [7.49 +/- 1.63 to 11.32 +/- 1.80 (SE) pmol/ml and 6.05 +/- 2.55 to 10.38 +/- 7.20 pmol/ml; P = 0.049, exercise] at SL and AA, respectively, but not at CA (P = 0.039, altitude). Similarly, PRA and ALDO rose from rest to postexercise (P < 0.001, exercise), but the rise in ALDO with exercise was less during AA than during SL and CA (P = 0.002, phase). The decreased ANP levels during exercise after altitude acclimatization, with no change in PRA and ALDO, suggest that ANP has little effect on PRA and ALDO under these conditions.

Effects of ibopamine on renal haemodynamics in patients with severe congestive heart failure.

The effects of a single dose of ibopamine on renal haemodynamics, sodium excretion, blood pressure (BP) and heart rate (HR) were investigated in 10 patients (aged 52-82 years) with severe congestive heart failure (CHF) who were in NYHA class IV. All patients used ACE inhibitors, digoxin and diuretics. After determining baseline values, ibopamine 100 mg was administered. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured simultaneously using radio pharmaceuticals. An increase in GFR and ERPF was observed during 3 and 2 h, with a maximum of 15 and 11%, respectively. The ratio GFR/ERPF representing the filtration fraction (FF) was markedly elevated at baseline, 34%, and remained unchanged. No clinically significant increase of sodium excretion was found. No changes in blood pressure, heart rate, plasma renin activity (PRA) and aldosterone or norepinephrine were observed. We conclude that ibopamine increases both ERPF and GFR in patients with severe CHF, possibly as a consequence of both inotropic cardiac and specific renal effects with equal preglomerular and postglomerular vasodilation. The lack of the presumed fall in FF may be the consequence of the expected DA1-induced renal vasodilation, partially reversed by the alpha adrenergic properties of ibopamine for this dose. Ibopamine caused no clinically significant natriuresis in these salt-depleted patients. No changes in PRA, aldosterone and catecholamines were found.

Disparity between blood pressure and PRA inhibition after administration of a renin inhibitor to anesthetized dogs: methodological considerations.

A dissociation between changes in blood pressure (BP) and plasma renin activity (PRA) has been noted after administration of renin inhibitors. In the present study, the renin inhibitor PD 132002 was given to salt-deplete, anesthetized dogs. PRA was measured at pH 6.0 by a conventional angiotensin I (ANG I) RIA method (PRA-C) and by an ANG I antibody-trapping RIA method (PRA-AT) performed at pH 7.4. PD 132002 at 0.01, 0.1, 1, and 10 mg/kg IV, reduced BP by 3 +/- 2, 9 +/- 2, 24 +/- 4, and 39 +/- 4 mm Hg, respectively, (baseline of 136 +/- 8 mm Hg, N = 5), when infused IV over 30 minutes with a 30 minute recovery between doses. The BP response at 10 mg/kg equaled that of saralasin (20 micrograms/kg/min IV). PRA-AT (baseline of 20 +/- 6 ng ANG l/ml/hr, N = 4) was inhibited by 0%, 28% +/- 12%, 75% +/- 10%, and 97% +/- 1% at 0.01, 0.1, 1, and 10 mg/kg, respectively. Plasma concentrations of immunoreactive ANG II were also reduced dose-dependently and paralleled changes in BP. In contrast, PRA-C (baseline of 13 +/- 4 ng ANG l/ml/hr, N = 4) was inhibited by 82% +/- 8% at 0.01 mg/kg and by > 98% at higher doses. After a single dose of PD 132002 at 10 mg/kg infused over 30 minutes, BP recovery paralleled changes in immunoreactive ANG II and PRA-AT, yet PRA-C inhibition showed no recovery over the same time course. Our data support the conclusion that BP relates better to PRA-AT than PRA-C. Thus the dissociation sometimes observed in studies with renin inhibitors between changes in BP and PRA may be attributed to the assay used to determine PRA.