Renin Release In Response Research Articles

The influence of vinblastine and colchicine on renin secretion in vivo and in vitro.

The effect of the microtubule inhibitors colchicine and vinblastine on renin release in vivo and in vitro was studied. Injection of 0.5 mg/100 g i.v. of colchicine or vinblastine to furosemide treated rats on a low salt diet resulted in a decrease of plasma renin as well as plasma angiotensinogen concentration during a 5 h observation period. Renin release from rat kidney slices was diminished by vinblastine (5 x 10(-5) M), when basal or stimulated (by isobutylmethylxanthine and isoproterenol) renin release was measured. Colchicine at 5 x 10(-5) M had no effect under these conditions. Renin release from the isolated perfused rat kidney was increased 2--3 fold by vinblastine (10(-5) M) or colchicine (10(-4) M). The maximal response of renin release to isoproterenol (10(-7) M) was not changed when vinblastine (10(-5) M) or colchicine (10(-4) M) were present in the perfusion medium. The contrasting results cast considerable doubts on the suitability of microtubule inhibitors in studies on renin secretion.

Renin release and pressor response to renal arterial hypotension: effect of dietary sodium

Changes in plasma renin activity (PRA) and mean arterial pressure (MAP) produced by renal arterial hypotension were studied in conscious, adrenalectomized dogs maintained on low-, normal-, or high-Na diet during constant steroid replacement therapy. In animals maintained on a low-Na diet, reduction of renal perfusion pressure to 50 mmHg for 45 min increased MAP 40 +/- 3 (SE) mmHg, while PRA rose rapidly by 36.5 +/- 6 ng ml-1 h-1. Similar renal hypotension in dogs maintained on a normal-Na diet increased MAP only 21 +/- 3 mmHg while PRA rose 5.5 +/- 0.9 ng ml-1 h-1; dogs on high-Na intake had a 6 +/- 1 mmHg pressure rise without a significant change in PRA. The rise in MAP correlated well with the log deltaPRA. Calculated open-loop gain was -1.2, -0.7, and -0.1 in dogs on low-, normal-, and high-Na diets, respectively. Nonpeptide angiotensin I converting enzyme inhibitor (CEI) reversed the elevated MAP observed during reduction of renal perfusion pressure in dogs on low- and normal-Na diets, but had little effect in dogs on high-Na intake. These observations suggest that the renin-angiotensin system becomes quantitatively more important in the regulation of blood pressure as Na intake is reduced.

The role of calcium in renin secretion from the isolated perfused cat kidney.

1. Isolated cat kidneys were perfused in situ with Locke solution and renin release in response to isoprenaline was studied. 2. Perfusion with isoprenaline produced a concentration-dependent enhancement of renin secretion. Increasing the concentration of stimulant also prolonged the duration of the secretory response. 3. After a 10 min exposure to isoprenaline (0-3 micrometer), there was a rapid facilitation of renin release which diminished after 10-30 min, followed by a second transient increase which declined over the next 40-60 min. Cycloheximide did not prevent augmented release when added together with the isoprenaline but did produce a reversible inhibition of the late phase when added 10 min after the isoprenaline. 4. Omission of calcium from the perfusion medium failed to depress the renin release induced by isoprenaline, glucagon, or furosemide. However, during prolonged calcium deprivation, the cycloheximide-sensitive phase of isoprenaline-evoked release was depressed. 5. The calcium antagonist D-600 failed to block the early phase of isoprenaline-induced renin secretion but inhibited the late phase of secretion. 6. Calcium alone elicited an explosive discharge of renin when added after a prolonged period of calcium-free perfusion. 7. These results support the view that extracellular calcium does not play an essential role in the mechanism of renin secretion from the renal juxtaglomerular cells, but that an increased influx of this cation is needed for synthesis and/or mobilization of the enzyme. It is tentatively proposed that the release of calcium from intracellular storage sites may be the signal which triggers renin secretion.

Plasma renin activity and blood corticosteroids in the Australian lungfish Neoceratodus forsteri.

Plasma renin activity (PRA) and blood aldosterone and deoxycorticosterone levels were measured in Australian lungfish. Plasma renin activity was depressed after intravenous infusions of iso-osmotic (0-6%) NaCl but not after hypo-osmotic (0-3%) infusions. The presence of PRA in this fish is consistent with prior reports of renal renin activity in other sarcopterygian fishes. The results of the infusion experiments suggest that a fall in plasma osmolality or electrolyte concentrations may oppose the reduction in renin release in response to volume expansion. Aldosterone and deoxycorticosterone were identified in the blood of Neoceratodus. The concentrations of both appeared higher in females than in males. Infusions of [5-valine]-angiotensin II amide for 2-4 h at rates known to increase blood pressure in this species did not alter blood aldosterone concentrations. This negative finding may suggest that the renin/angiotensin system is not involved in aldosterone regulation in Neoceratodus or that angiotensin receptors involved in regulation of steroidogenesis have a greater specificity for endogenous angiotensin than do vascular receptors.

Effects of renal denervation on renin release in response to tilting and furosemide.

In anesthetized cats head-up tilting for 30 min and infusion of furosemide at 0.75 mg/kg in 30 min significantly raised renin release from the innervated kidney (increments of 90.7 +/- 21.4 ng/min on tilting and 105.4 +/- 26.4 ng/min after furosemide); a small and inconstant increase from the contralateral denervated kidney (increments of 16.8 +/- 16.0 and 16.3 +/- 17.7 ng/min, respectively) was abolished by acute bilateral adrenalectomy. Larger doses of furosemide (6.0 mg/kg) could release renin from the denervated kidney also, but the response was still more marked on the innervated side especially in the early period of infusion (increments of 132.7 +/- 23.8 and 33.7 +/- 23.8 ng/min of innervated and denervated sides at 10 min). The response of the denervated kidney to 6.0 mg furosemide/kg was not affected by adrenalectomy. Stimulation of juxtaglomerular cells by tilting is entirely due to sympathoadrenergic activation; stimulation by furosemide is also entirely neural when the diuretic drug is given in moderate doses, but is partly independent of innervation when larger doses are administered.

Control of renin secretion.

The present study was designed to examine the interrelationship between the intrarenal vascular receptor and the sympathetic nerve, beta-adrenergic system, for renin secretion in the anesthetized dog. 1) A reduction in renal arterial pressure from a control pressure to 100 mmHg changed neither ther flow rates of all cortex zones nor renin secretion. Further reduction of renal arterial pressure to 75 mmHg resulted in a significant increase of renin secretion and a decrease of blood flow in the outer cortex. Intrarenal arterial infusion of norepinephrine at a control pressure increased a renin secretion. However, norepinephrine infusion at a reduced pressure suppressed the renin release with a recovery of the vascular resistance to the control level. These results suggest that the changes in the degree of blood flow and pressure in the renal afferent arterioles are not essential for the renin secretion,but renin secretion by the pressure reduction might be related to the autoregulatory capacity of afferent arterioles in the outer cortex. 2) At 5 min of hemorrhagic period (75 mmHg) arterial PRA elevated in control, and phenoxybenzamine and propranolol treated groups and any significant difference in responses was not observed among groups. However, at 60 min of hemorrhagic hypotensive period PRA in control and phenoxybenzamine treated groups further increased, but PRA in propranolol treated group was not alter from its 15 min value. These results indicated that the roles of vascular receptor and renal sympathetic nervous sytem in receptor and renal sympathetic nervous system in renin secretion might be separated, and that the renal sympathetic nervous system did not relate to the early response of renin release, but related to the late response. 3) Intrarenal arterial infusion of cAMP and DbcAMP resulted in a significant increase of renin release. In addition, CaC12 solution was infuesed into the renal artery and a significant rise in renal venous PRA was observed within 5 min of infusion. These data suggested that a beta-adrenergic receptor-adenyl cyclase-cAMP system was involved in the control of renin secretion, and that since the intracellular effect of cAMP was partly related to the change of intracellular Ca distribution, its change resulted in an increase in renin secretion.

Specificity of blockade of renal renin release by propranolol in the cat.

1. The anaesthetized cat, unilaterally nephrectomized and with renal nerves sectioned, has been used in a study of the specificity of the inhibitory effect of propranolol on renin release. 2. The effect of (+)-propranolol on the rise in plasma renin activity (PRA) induced by renal nerve stimulation has been examined. When administered at approximately the same dose as the racemic mixture which blocks renin release in response to this stimulus, (+)-propranolol did not significantly reduce the magnitude of the response. Therefore the action of racemic propranolol in blocking the response to neural stimulation can be attributed to the (−)-isomer. 3. Renal artery constriction, producing blood flow changes similar to those resulting from renal nerve stimulation, also induces a rise in PRA. (±)-Propranolol, in amounts which block the rise in PRA observed with renal nerve stimulation, did not prevent the increase seen with renal artery constriction. 4. Reduction of renal perfusion pressure within the autoregulatory range for 20 min resulted in a rise in PRA in all experiments. (±)-Propranolol did not significantly affect the response. 5. It is concluded that the release of renin in response to renal nerve stimulation cannot be attributed to associated changes in renal blood flow. The evidence is compatible with a direct action of the neurotransmitter on renin-containing cells via a β-adrenergic receptor. When renin release is induced by non-adrenergic mechanisms propranolol blockade has no significant effect on the response.

Impaired autoregulation of blood flow and glomerular filtration rate in the isolated dog kidney depleted of renin.

The effect of renin depletion on autoregulation of renal blood flow and glomerular filtration rate was examined in an isolated perfused kidney preparation. Group 1 dogs received a normal-sodium diet, group 2 dogs received deoxycorticosterone acetate (DOCA) and a high-sodium diet, group 3 dogs received DOCA and a sodium-deficient diet, group 4 dogs received a high-sodium diet without DOCA, and dogs in groups 5 and 6 were treated just like dogs in groups 1 and 2, respectively. Renin release was stimulated by decreasing renal arterial pressure to 50 mm Hg. An increase in renal arterial pressure from 100 to 160 mm Hg was associated with an impaired autoregulatory response in kidneys from group 2 dogs and in two kidneys from group 4 dogs; these kidneys exhibited suppressed or absent renin release in response to a decrease in renal arterial pressure. A separate group of experiments demonstrated that DOCA plus a high-sodium diet completely depleted the kidney of renin stores, indicating that decreased renin secretion reflected depletion of renal renin content. Infusing angiotensin II (0.22 ± 0.06 µg/min) into the renal artery of group 2 kidneys did not normalize the autoregulatory response. A decrease in renal arterial pressure from 150 to 50 mm Hg was associated with impaired autoregulation of glomerular filtration rate and renal blood flow in kidneys from group 6 dogs; renin secretion was undetectable in these kidneys. All kidneys from groups 1, 3, and 5 and the remaining six kidneys from group 4 exhibited a normal autoregulatory response and normal renin release. In groups 1-3, zonal blood flow was measured using the radiolabeled microsphere technique. Only in group 2 did a significant redistribution of fractional blood flow from the inner to the outer cortex occur. These experiments demonstrate that renin depletion impairs the capacity of the kidney to autoregulate blood flow and glomerular filtration rate; thus the data are consistent with the hypothesis that the renin-angiotensin system participates in the autoregulatory response.

Renin release responses to acute alterations in renal arterial osmolarity.

Renin release responses to acute alterations in renal arterial osmolarity.

Effect of propranolol and theophylline on renin release caused by furosemide in the cat

Pretreatment with propranolol did not significantly modify the marked increase in plasma renin activity (PRA) produced by furosemide administration in anaesthetized, renally-denervated cats. Treatment with propranolol alone significantly lowered PRA. Theophylline, administered i.v. at the human therapeutic dose of 7 mg/kg, did not affect the level of PRA. When theophylline was superimposed on furosemide no potentiation of the effect on PRA was observed. Conversely, when furosemide was superimposed on theophylline the effect was similar to that produced by furosemide alone. These results indicate that, in contrast to neural stimulation, the release of renin in response to furosemide is not propranolol sensitive. Further, they suggest that the release of renin, in the renally-denervated cat, is not mediated through cyclic AMP, if the therapeutic level of theophylline effectively inhibits phosphodiesterase in the kidney.

Release of prostaglandin-like material from dog kidney during nerve stimulation

Canine kidneys were autoperfused in situ at constant flow in 28 experiments. Renal venous effluent was examined for (PLM) prostaglandin-like material following acidic lipid extraction and thin layer chromatography or by continuous bioassay utilizing the bloodbathed organ technique. There was a low basal efflux of PLM from the kidney which was markedly enhanced during the renal vascular constriction elicited by renal nerve stimulation at 2-10 cycles/second or by infusion of norepinephrine. The PLM was tentatively identified as an E-type prostaglandin based on chromatographic behavior and bioassay. The present study indicates that PLM is released from the dog kidney during an increase in renal vascular resistance. Release is not necessarily dependent upon changes in total renal blood flow although alterations in the distribution of intrarenal blood flow might be involved. (authors)