Effects of right atrial stretch on plasma renin activity.

In anaesthetized dog, right atrial stretch leads in the first five minutes to a decrease in plasma renin activity, when measured in inferior vena cava just above the renal veins. Bilateral cervical vagotomy increases plasma renin activity. After vagotomy, atrial stretch no longer has any effect on plasma renin activity. The results support the hypothesis of a control of renin secretion originating from atrial volume receptors.     

Regulation of plasma vasopressin and renin activity in conscious hindlimb-unloaded rats

Cardiovascular deconditioning occurs in astronauts after spaceflight or in individuals subjected to bed rest. It is characterized by an increased incidence of orthostatic intolerance. The mechanisms responsible for orthostatic intolerance are likely multifactorial and may include hypovolemia, autonomic dysfunction, and vascular and cardiac alterations. The arterial baroreflex is an important compensatory mechanism in the response to an orthostatic stress. In a previous study, we demonstrated that arterial baroreflex mediated sympathoexcitation was blunted in hindlimb-unloaded (HU) rats, a model of cardiovascular deconditioning. The arterial baroreflex also contributes to the regulation of vasoactive hormones including vasopressin and angiotensin II. In the present study, we tested the hypothesis that the neurohumoral response to hypotension is also attenuated in rats after 14 days of hindlimb unloading. To test this hypothesis, the vasodilator diazoxide (15 or 25 mg/kg) or saline (0.9%) was administered to produce hypotension or control conditions, respectively, in conscious HU and control rats. Plasma samples were collected and assayed for vasopressin and plasma renin activity (PRA). Diazoxide (25 mg/kg) produced significant increases in vasopressin and PRA compared with saline controls. HU rats exhibited significantly higher levels of vasopressin at rest and the increase in vasopressin levels during hypotension was enhanced by hindlimb unloading. Neither resting nor hypotension-induced PRA was altered by hindlimb unloading. These data suggest that although baroreflex-mediated sympathoexcitation is blunted by hindlimb unloading, hypotension-induced vasopressin release is enhanced and hypotension-induced PRA is unaffected. Increased circulating vasopressin may serve to compensate for blunted baroreflex regulation of sympathetic nervous activity produced by hindlimb unloading or may actually contribute to it.     

Nifedipine inhibits the hypoxia-induced decrease in plasma renin activity in conscious dogs.

Acute hypoxia induces a decrease in plasma renin activity (PRA), mediated, e.g., by an increase in adenosine concentration, calcium channel activity, or inhibition of ATP-sensitive potassium channels. The decrease in PRA results in a decrease in angiotensin II (AngII) and plasma aldosterone concentration (PAC). This study investigates whether these hypoxia-induced mechanisms can be inhibited by the L-type voltage-dependent calcium channel antagonist nifedipine. Eight conscious, chronically tracheotomized dogs received a low sodium diet (0.5 mmol Na x kg body wt(-1) x day(-1)). The dogs were studied twice in randomized order, either with nifedipine infusion (1.5 microg x kg body wt(-1) x min(-1), Nifedipine) or without (Control). The dogs were breathing spontaneously: first hour, normoxia [inspiratory oxygen fraction (FiO2)=0.21]; second and third hour hypoxia (FiO2=0.1). In Controls, PRA (6.8+/-0.8 vs. 3.0+/-0.5 ngAngI x ml(-1) x min(-1)), AngII (13.3+/-1.9 vs. 7.3+/-1.9 pg/ml), and PAC (316+/-50 vs. 69+/-12 pg/ml) decreased during hypoxia (P<0.05). In Nifedipine experiments, PRA (6.5+/-0.9 vs. 10.5+/-2.4 ngAngI x ml(-1) x min(-1)) and AngII (14+/-1.1 vs. 18+/-3.9 pg/ml) increased during hypoxia, whereas the decrease in PAC (292+/-81 vs. 153+/-41 pg/ml) was blunted (P<0.05). These results foster the idea that the hypoxia-induced decrease in PRA involves L-type calcium channel activity.     

Beta-adrenoreceptor blockade in the conscious rabbit: effects on plasma renin activity and blood pressure.

The administration of a single dose of dl-propranolol, 1 mg/kg i.v., in the conscious unstimulated rabbit produced effective beta-adrenoreceptor blockade (inhibition of isoprenaline tachycardia) for 150 min. During this period there was a positive correlation between plasma concentrations of propranolol and the degree of beta-blockade observed. In a further group of animals treated with propranolol, plasma renin activity (PRA) fell to 50% of control (P < 0.001) within 60 min, the rate of change of PRA also correlating with plasma propranolol levels. Similarly, there were reductions in mean blood pressure (P < 0.025) and heart rate (P < 0.025). Statistical relationships between the fall in blood pressure and either pre-treatment PRA or the change in PRA were consistent with the hypothesis that the hypotensive effect of propranolol was dependent upon its suppression of renin release. However, an alternative possibility that the fall in blood pressure was due to an acute reduction in cardiac output could not be excluded.     

Effect of atrial natriuretic factor on plasma vasopressin in conscious rats

An intravenous (IV) bolus injection (10 μg) of synthetic rat atrial natriuretic factor [ANF (Arg 101-Tyr 126)] into normal conscious Sprague-Dawley rats produced a significant decrease of plasma arginine vasopressin (AVP) while 1-, 2-, and 5-μg doses exerted no such effect. Mean arterial blood pressure (MAP) was lowered about 15 mmHg by an IV 10 μg bolus injection of ANF. When plasma AVP rose significantly in rats exposed to such osmotic stimuli as 600 mM NaCl and 900 mM mannitol intraperitoneally (IP), subsequent IV injection of ANF (10 μg) markedly depressed this parameter. Lower doses of ANF were ineffective against 600 mM NaCl IP. The significant elevation of plasma AVP levels by hypertonic sucrose 900 mM IP was not modified by ANF (10 μg). Blood pressure remained unchanged after IP administration of various osmotic stimuli, except mannitol, and in all these experiments an IV bolus of ANF exerted a lowering effect on MAP. Seventy-two hr water deprivation (mixed osmotic and volume stimulus) resulted in elevated plasma AVP levels which were unaffected by an IV bolus injection of ANF at doses of 0.06–10 μg. Immunoreactive ANF (IR-ANF) rose in plasma to 39.3±13 ng/ml 1 min after an IV bolus injection of 10 μg ANF, dropping to 1.01±0.2 ng/ml after 5 min and to 0.32±0.01 ng/ml after 10 min (when ANF and AVP interactions were studied), but still remained approximately six times higher than in control rats. These results suggest that, in the conscious rat, only pharmacological levels of ANF observed after an IV bolus infusion may influence both resting and osmotically-stimulated AVP levels.     

Effect of somatostatin on plasma renin activity.

Intravenous infusion of somatostatin in mongrel dogs caused a significant decrease in the peripheral plasma renin activity (PRA) enhanced by pentobarbital sodium anesthesia or furosemide treatment. However, the inhibitory activity vanished within 10 min after termination of somatostatin infusion. Intrarenal arterial infusion of somatostatin decreased furosemide-enhanced PRA in renal vein by 24.0%, 16.6% and 8.6% in dose of 0.1, 0.5 and 1.0 microgram, respectively. On the other hand, high doses of the peptide (50-200 microgram) failed to decrease. The changes in PRA occurred in the absence of any alteration in blood pressure during the intravenous infusion under furosemide treatment. In an in vitro study, the addition of somatostatin in doses of 0.01 and 0.05 microgram suppressed the renin release in dog renal cortical cell suspension by 74.3% and 53.6%, respectively. Therefore, in both intrarenal arterial infusion and the cell suspension system, somatostatin was increasingly effective in decreasing renin release towards the lower end of the dose range tested. These results suggest that the effect of somatostatin on hyperreninemia may involve an inhibition of renin release at the cell level in the kidney.     

The influence of plasma renin substrate on the relationship between plasma renin activity and plasma renin concentration. An experimental study in hyper- and hypothyroid rats

The effects of endogenous Plasma Renin Substrate (PRS) on the relationship between Plasma Renin Activity (PRA) and the Plasma Renin Concentration (PRC) have been studied in hyperthyroid rats, by I-triiodothyronine (T3) administration and in hypothyroid rats, by propylthiouracil (PTU) treatment, to clarify if PRA changes are an adequate index for evaluating the renin-angiotensin changes during the alterations in the thyroid function. Although in experimental situations studied the induced variation on PRC explains a 62 per cent of the changes in PRA, finding a good lineal correlation between both parameters (r = 0.79, P less than 0.001). Not only does PRS play an important role on the kinetic of the enzymatic reaction but also explains jointly with PRC up to a 85 per cent of PRA alterations. PRS changes become more important during thyrotoxicosis where they limit in a higher degree the velocity of reaction due to inverse relationship between PRC and PRS (r = 0.74, P less than 0.001).     

Effects of changes in circulating volume and in arterial pressure on plasma renin activity in the intact rat

The effects of changes in arterial pressure and in circulating volume on Plasma Renin Activity (PRA) in the intact rat were compared by two experimental procedures. Gradual volume depletion was induced by intraperitoneal injection of a hyperoncotic polyethyleneglycol solution (PEG) in absence of acute changes in Systolic Arterial Pressure (SAP). SAP was measured in the conscious state by the tail cuff technique. Plasma Protein Concentration (PPC) and Hematocrit (Hct) increases after PEG injection were compared as the index for measuring the Plasma Volume Reduction (PVR). PRA showed a significant (p less than 0.001) linear relationship with PPC, suggesting a direct dependence of renin secretion on volume depletion. Acute changes in the circulating volume were induced by controlled hemorrhages of 5.0, 10.0, 15.0 and 20.0 ml of blood/kg body weight. The increase in PRA showed a significant relationship with the changes in circulating volume, but it did not show any dependence on the changes in Mean Arterial Pressure (MAP). Our results suggest that, in the intact and conscious rat, renin secretion responds to the information from the cardiopulmonary volume receptors rather than to that from the high pressure receptors.     

Influence of age on orthostatic changes in plasma renin activity and urinary catecholamines in man.

The authors studied plasma renin activity (PRA), urinary epinephrine, norepinephrine and dopamine excretion and their mutual relationships in 54 healthy subjects under basal (recumbent) conditions and age-related orthostatic changes in these parameters. The test subjects were divided into six 10-years groups, according to their year of birth (1901-1910 to 1951-1960). In the oldest groups (1901-1910 and 1911-1920), both basal PRA values and norephrine and epinephrine excretion and their postural increase were smaller than in younger subjects. Conversely, urinary dopamine excretion and the dopamine/norepinephrine and epinephrine ratio rose with advancing age. There were no significant differences between the plasma sodium and potassium concentrations in the various groups. Urinary aldosterone excretion was slightly higher in the oldest group than in the others, but was still within the control value limits. The intravenous administration of Inderal reduced both resting PRA values and the orthostatic increase in the youngest age groups, so that their PRA approached the values in older subjects. Higher norepinephrine and epinephrine excretion and the lower dopamine/norepinephrine and epinephrine in young subjects may play a role in their higher PRA, especially in the orthostatic reaction. Diminution of sympathetic activity, with lower norepinephrine and epinephrine excretion and relatively high dopamine excretion, may have a direct bearing on the lower PRA values in older subjects. The diminished capacity of older subjects for catecholamine mobilization and raised renin secretion during an orthostatis stress may be related to the higher incidence of orthostatic forms of hypotension in old age.     

Capsaicin-sensitive nerves influence the release of atrial natriuretic factor by atrial stretch in the rat.

Although many factors may modulate the release of atrial natriuretic factor (ANF), the primary mechanism has been demonstrated to be atrial stretch. Recent studies have led to the suggestion that the peptidergic innervation of the heart, through the release of peptides, may be involved in the control of ANF secretion. We have examined the influence of chronic capsaicin treatment on three models of atrial stretch that release ANF. This treatment inhibited ANF released through in vivo blood volume expansion and through balloon inflation in the right atrium of in vitro isolated perfused hearts. Immunohistochemical and electron microscopical analysis confirmed the absence of innervation of the heart by calcitonin gene related peptide and substance P immunoreactive nerve fibres and apparent lack of effect on atrial granules in capsaicin treated rats. We conclude that capsaicin-sensitive cardiac innervation is a component modulating the release of ANF, stimulated by atrial stretch in the rat.     

Influence of season on plasma antidiuretic hormone, angiotensin II, aldosterone and plasma renin activity in young volunteers

We investigated seasonal changes in hormonal and thermoregulatory responses. Eight volunteers were subjected to the experiment at four times of the year: around the vernal and autumnal equinoxes, and at the summer and winter solstices at latitude 35° N. Plasma antidiuretic hormone (ADH), angiotensin II (ANG II), aldosterone (ALD) and plasma renin activity (PRA) were analyzed before and after water immersion. Seasonal changes in thermoregulatory responses were assessed by measuring core temperature and sweat rate during immersion of the leg in hot water (at 42°C) for 30 min in a room maintained at 26°C. The concentration of plasma ADH and ALD before water immersion was significantly higher in summer than in other seasons. The concentrations of ANG II and PRA did not show seasonal variations. Changes in tympanic temperature during water immersion showed significant differences between seasons, and were higher in winter than in other seasons. The sweat rate was significantly higher in summer than in other seasons. In summary, ADH and ALD concentrations displayed a seasonal rhythm with marked elevation in summer; this may be a compensative mechanism to prevent dehydration from increased sweat loss during summer due to heat acclimatization.     

Effect of parathyroid hormone on plasma renin activity in humans

The effect of PTH infusion on PRA was evaluated in 22 normotensive subjects. Intravenous infusion of PTH produced an increase in PRA in studied subjects. This increase in PRA was dose dependent from 1.505 +/- 0.226 to 2.500 +/- 0.346 nmol/l/hour after administration of 100 units of PTH and from 1.648 +/- 0.189 to 4.294 +/- 0.614 nmol/l/hour after 200 units of PTH and was markedly decreased by a beta blocking drug from 1.660 +/- 0.259 to 2.498 +/- 0.485 nmol/l/hour. These responses were observed without any significant changes in plasma calcium and blood pressure. From our results we can conclude that PTH increases PRA in normotensive controls. This effect is partly blocked by beta adrenergic blockers.     

Antisera to atrial natriuretic factor reduces urinary sodium excretion and increases plasma renin activity in rats

Although the presence of atrial natriuretic factor in the blood has been demonstrated by radioimmunoassay, its biological activity and physiological significance has not been elucidated. Using specific antiserum against atrial natriuretic factor, we investigated the effect of passive immunization in rats. A significant reduction of urine output and urinary sodium excretion lasted for about 30 min after intravenous administration of antiserum. The effects were more pronounced in rats pretreated with deoxycorticosterone acetate and saline. Plasma renin activity was increased after the administration of antiserum. No significant effects on the urinary sodium excretion was observed following injection of normal rabbit serum. The results of this study provide evidence indicating that endogenous atrial natriuretic factor plays an important role in the regulation of urinary water and sodium excretion and plasma renin activity.     

Influence of sedentary versus physically active conditions on regulation of plasma renin activity and vasopressin

Physical inactivity is an independent risk factor for cardiovascular disease. Sedentary animals compared to physically active controls exhibit enhanced sympathoexcitatory responses, including arterial baroreflex-mediated sympathoexcitation. Hypotension-induced sympathoexcitation is also associated with the release of vasoactive hormones. We hypothesized that sedentary conditions may enhance release of the vasoactive hormones AVP and ANG II. To test this hypothesis, the humoral response to hypotension was examined in conscious rats after 9-12 wk of sedentary conditions or "normally active" conditions. Normally active conditions were produced by allowing rats access to running wheels in their home cages. Running distance peaked after 4 wk (4.5 +/- 0.7 km/day), and the total distance run after 9 wk was 174 +/- 23 km (n = 25). Similar levels of hypotension were induced in conscious sedentary or physically active animals with the arterial vasodilator, diazoxide (25 mg/kg iv). Control experiments used a saline injection of equivalent volume. Plasma samples were collected and assayed for plasma AVP concentration and plasma renin activity (PRA). Sedentary conditions significantly enhanced resting and hypotension-induced PRA relative to normal physical activity. In contrast, resting and hypotension-induced AVP levels were not statistically different between groups. These data suggest that baroreflex-mediated activation of the renin-angiotensin system, but not AVP secretion, is enhanced by sedentary conditions. We speculate that augmented activation of the renin-angiotensin system may be related to enhanced sympathetic outflow observed in sedentary animals and may contribute to increased risk of cardiovascular disease in the sedentary population.