Effect of intrarenal arterial infusion of magnesium on renin release in dogs.

Magnesium chloride was infused into the renal artery of anesthetized dogs in order to determine its effect on renal function. Natriuresis and diuresis were observed during MgCl2 infusion, but there appeared to be no effect on glomerular filtration rate (GFR), or plasma sodium or potassium concentrations. Although mean arterial blood pressure and renal plasma flow (RPF) decreased throughout the experiment, the fall was not significant until after stopping MgCl2 infusion. A significant stimulation of renin secretion occurred during magnesium administration.     

Effect of clonidine on three types of experimental hypertension and on plasma renin activity in dogs]

Intra-cisternal clonidine (3 microgram/kg) reduced hypertension and cardiac acceleration after defrenation in dogs, but did not act in intra-venous infusion (10 microgram/kg). The renin activity was not modified. Clonidine was always inactive on hypertension after stimulation of visceral afferences or after injection of potassium cyanidine. These results show that a central mechanism was implied in the anti-hypertensive action of clonidine.     

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.     

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.     

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.     

Effect of head-down tilt on basal plasma norepinephrine and renin activity in humans

The effects of loading cardiopulmonary baroreceptors on basal norepinephrine and renin activity were studied in six normal subjects. Loading of cardiopulmonary baroreceptors was accomplished by a 60-min 30 degrees head-down tilt with small supplemental saline infusions. Central venous pressure was measured continuously by intrathoracic catheter; arterial pressure was measured indirectly by cuff. During the tilt, central venous pressure increased from 5.1 +/- 1.3 to 8.9 +/- 1.7 mmHg (P less than 0.001), whereas arterial pressure was unchanged. Plasma norepinephrine (185 +/- 85 pg/ml) and plasma renin activity (3.9 +/- 5.7 ng . ml-1 . h-1) did not change. Moderate sustained loading of cardiopulmonary baroreceptors is therefore without effect on unstressed plasma norepinephrine and renin activity in normal humans, suggesting that the tonic inhibitory effects of these receptors on these neurohumoral control systems are not readily increased in the basal state.     

Effect of pertussis toxin on the adrenergic regulation of plasma renin activity

Basal plasma renin activity (PRA) was not modified by pertussis toxin administration. On the contrary, the modulation of PRA by adrenergic amines was markedly affected by the toxin. Administration of epinephrine did not modified PRA in the controls but markedly increased it in toxin-treated rats. This effect of epinephrine was reproduced in control rats when yohimbine was given before the catecholamine. Clonidine decreased PRA to a much more significant extent in control rats than in animals treated with the toxin. Isoproterenol stimulated PRA to a greater level in toxin-treated rats. Our data indicates that pertussis toxin blocks the alpha 2-adrenergic modulation of renin release and magnifies the ability of beta adrenergic activation to stimulate PRA.     

Effect of cyclooxygenase and thromboxane synthetase inhibition on furosemide-stimulated plasma renin activity

We studied the effects of a specific thromboxane (TX) synthetase inhibitor (U-63,557A) and a cyclooxygenase inhibitor on furosemide-induced renin release. Furosemide (2.0 mg X kg-1) was injected into Sprague-Dawley rats pretreated with indomethacin (10 mg X kg-1, i.v.), U-63,557A (1.0-32.0 mg X kg-1, i.v.), or vehicle (Na2CO3 0.03 M). Plasma renin activity was measured in blood samples collected 0, 10, 20, and 40 min after the injection of furosemide. Blood was also collected after the administration of vehicle, indomethacin, or U-63,557A for serum TXB2, a measure of platelet TXA2 synthesis. The results demonstrated that plasma renin activity rose with time following furosemide in the various groups of rats; indomethacin suppressed the furosemide-induced increments in plasma renin activity, while U-63,557A at doses of 4-8 mg X kg-1 augmented it. At doses below 4 mg X kg-1 or above 8 mg X kg-1, U-63,557A did not augment renin secretion. Indomethacin and U-63,557A reduced serum thromboxane by 81 and 90%, respectively. Thus, these experiments suggest that thromboxane synthetase inhibition, within a narrow dosage range, potentiates furosemide-induced renin release while cyclooxygenase inhibition suppresses it.     

Role of plasma renin activity and the renal nerves in the natriuresis of L-NMMA infusion in rats

The objective of this study was to determine the effect of N(G)-monomethyl-L-arginine (L-NMMA) infusion on plasma renin activity (PRA) in the presence or absence of the renal nerves in normotensive Wistar-Kyoto (WKY) rats and Okamoto spontaneously hypertensive rats (SHR). All rats were unilaterally nephrectomized two weeks before the acute experiment. On the day of the experiment, acute renal denervation (Dnx) of the remaining kidney was performed in one group of WKY rats (Dnx-WKY; n= 10) and one group of SHRs (Dnx-SHR: n=7). The renal nerves were left intact in a group of WKY rats (Inn-WKY; n=8) and SHRs (Inn-SHR; n=9). After a control clearance period, L-NMMA was administered i.v. (15 mg/kg bolus followed by 500 microg/kg/min infusion) and another clearance period of 20 min was taken. In all experimental groups L-NMMA infusion resulted in a significant natriuresis. L-NMMA infusion increased fractional excretion of sodium (FE(Na)) to a greater extent in the Inn-SHR than in the Inn-WKY (delta FE(Na) = 5.23+/-0.87% vs delta FE(Na) = 2.87+/-0.73% respectively; P=0.05), PRA did not change in the SHR with the infusion of L-NMMA. However, in the Inn-WKY group, the natriuresis of L-NMMA infusion was associated with a tendency for lower PRA levels as compared to a group of time control Inn-WKY rats. In Dnx-WKY, the natriuresis of L-NMMA infusion (delta FE(Na) = 4.60+/-0.52%) was associated with a significantly lower level of PRA (4.26+/-1.18 ng AI/ml/hr) as compared to a group of time control Dnx-WKY rats (9.83+/-1.32 ng AI/ml/hr; P<0.05). In the Dnx-SHR, the natriuretic response to L-NMMA infusion was significantly attenuated by renal denervation (delta FE(Na) = 2.36+/-0.34%) and PRA was unchanged. In conclusion, the natriuretic effect of systemic inhibition of nitric oxide (NO) synthesis was associated with decreased PRA in the Dnx-WKY suggesting that a potential interaction exists between NO and the renal nerves in the modulation of PRA in the normotensive WKY rat. Whereas, the natriuretic effect of L-NMMA infusion in the SHR in the presence and absence of the renal nerves, were independent of changes in PRA.