Effects of Stimulation and Inhibition of the Renal Prostaglandin Synthetase System on Renin Release in vivo and in vitro

1976 ◽  
Vol 51 (s3) ◽  
pp. 271s-274s
Author(s):  
P. C. Weber ◽  
C. Larsson ◽  
M. Hamberg ◽  
E. Änggård ◽  
E. J. Corey ◽  
...  
Keyword(s):  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Renin Activity ◽  
Renin Release ◽  
Rabbit Kidney ◽  
Kidney Cortex ◽  
Acid Pretreatment ◽  
Prostaglandin Endoperoxide

1. The prostaglandin precursor arachidonic acid (C20:4) increases plasma renin activity in the rabbit and rat when it is infused into the renal arteries. 2. The increase in plasma renin activity after C20:4 in rats is not changed by volume expansion. 3. The inhibitor of prostaglandin synthesis indomethacin decreases plasma renin activity in the rabbit. 4. The increase in plasma renin activity after total renal ischaemia is abolished by pretreatment with indomethacin. 5. C20:4 increases dose- and time-dependent renin release from slices of rabbit kidney cortex. 6. Indomethacin or 5,8,11,14-eicosatetraynoic acid pretreatment in vivo, and addition to the incubation medium, reduces basal as well as C20:4-stimulated renin release in vitro. 7. The stimulating effect of C20:4 on renin release is assumed to be caused directly by formation of prostaglandin endoperoxides in the kidney cortex and not by prostaglandins since in vitro a natural prostaglandin endoperoxide (PGG2) and two stable synthetic prostaglandin endoperoxide analogues (EPA I and EPA II) do increase the release of renin, but PGE2 has no effect and PGF2α inhibits renin release.

Glyburide attenuates calmodulin antagonist-stimulated renin release from isolated mouse juxtaglomerular cells

1995 ◽  
Vol 269 (2) ◽  
pp. F242-F247 ◽  
Author(s):  
D. A. Linseman ◽  
J. A. Lawson ◽  
D. A. Jones ◽  
J. H. Ludens
Keyword(s):  
Calcium Release ◽  
Plasma Renin ◽  
Renin Activity ◽  
Renin Release ◽  
K Channel ◽  
Inhibitory Effects ◽  
Calmodulin Antagonist ◽  
Voltage Gated Calcium Channels

Previous reports have shown that K+ channel openers elevate plasma renin activity in vivo and stimulate renin release (RR) from juxtaglomerular (JG) cells in vitro. Therefore, we examined whether the K+ channel blocker, glyburide, inhibits basal RR or RR stimulated by elevating cAMP or by inhibiting Ca2+/calmodulin activity in cultures of isolated mouse JG cells. Glyburide treatment (10-300 microM) had no effect on basal RR, which measured approximately 10% or 30% of the total cellular renin activity after 4 or 24 h, respectively. RR stimulated by elevating cAMP with isoproterenol, forskolin, or 3-isobutyl-1-methylxanthine was also unaffected by glyburide. In contrast, glyburide significantly attenuated RR stimulated by the calmodulin antagonists, calmidazolium, trifluoperazine, and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). Calmidazolium-stimulated RR returned to basal levels with 100 microM glyburide cotreatment. Blockade of voltage-gated calcium channels with verapamil or inhibition of calcium release from intracellular stores with 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8) had no effect on the ability of glyburide to attenuate calmidazolium-stimulated RR. However, lowering of the extracellular calcium concentration by the addition of EGTA abolished the inhibitory effects of glyburide. We conclude that modulation of K+ channels may influence RR by affecting Ca2+/calmodulin-regulated secretion, but not cAMP-mediated secretion, from JG cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in plasma renin activity and aldosterone concentration in response to endothelin injection in dogs

1989 ◽  
Vol 121 (3) ◽  
pp. 361-364 ◽  
Author(s):  
Atsuhiro Otsuka ◽  
Hiroshi Mikami ◽  
Katsutoshi Katahira ◽  
Takeshi Tsunetoshi ◽  
Kaori Minamitani ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Total Peripheral Resistance ◽  
Inhibitory Action ◽  
Peripheral Resistance ◽  
Plasma Renin ◽  
Renin Activity ◽  
Renin Release ◽  
Renal Vasoconstriction

Abstract. The effects of endothelin on the renin-aldosterone system were examined by injecting it intravenously at low (40 pmol/kg) and high (400 pmol/kg) doses into pentobarbital-anesthetized dogs. Plasma renin activity and aldosterone concentration together with hemodynamic parameters were measured before and 60 min after endothelin injection. The lower dose of endothelin induced no significant increase in mean blood pressure or total peripheral resistance. It caused a slight decrease of plasma renin activity from 10.3 ± 1.6 to 5.9 ± 1.3 μg · l−1 · h−1 (p <0.1) and a decrease of aldosterone concentration from 364 ± 68 to 231 ± 58 ng/l (p <0.05) with an increase in total peripheral resistance (p <0.05), but it did not cause any clear change in the plasma renin activity or aldosterone concentration. Thus, endothelin increases the blood pressure mainly by vasoconstriction. The finding of a slight decrease in the plasma renin activity after the lower dose of endothelin, together with our previous finding that endothelin inhibits renin release from isolated rat glomeruli, suggests that endothelin inhibits renin release in vivo. With the higher dose of endothelin, stimulation of renin release secondary to renal vasoconstriction might have counteracted the direct inhibitory action of endothelin. The decrease in aldosterone concentration may have been due to the direct inhibitory action of endothelin on aldosterone release or it may be a secondary effect induced by suppression of plasma renin activity.

Effects of Angiotensinase Inhibitors on Plasma Protein Binding and IC50 Determinations of Renin Inhibitors

1992 ◽  
Vol 38 (11) ◽  
pp. 2239-2243 ◽  
Author(s):  
B D Dayton ◽  
H H Stein ◽  
J Cohen ◽  
W R Baker ◽  
S A Boyd ◽  
...  
Keyword(s):  
Plasma Renin Activity ◽  
Plasma Proteins ◽  
Proteinase Inhibitors ◽  
Plasma Renin ◽  
Renin Activity ◽  
Phenylmethylsulfonyl Fluoride ◽  
Renin Inhibitors ◽  
Ic50 Values

Abstract To establish whether the use of proteinase inhibitors in the routine determination of in vitro plasma renin activity overestimates the potency of renin inhibitors in vivo, we examined the effects of phenylmethylsulfonyl fluoride and 8-hydroxyquinoline sulfate on the binding to plasma proteins and the respective IC50 values (50% inhibiting concentrations) of three renin inhibitors. All three renin inhibitors, A-64662, A-65317, and A-74273, bound (&gt; 60%) to plasma proteins at both pH 6.0 and 7.4, with slightly greater binding at pH 7.4. Phenylmethylsulfonyl fluoride (1.45 mmol/L) had no significant effect on the protein binding at either pH 6.0 or 7.4; 8-hydroxyquinoline sulfate (3.4 mmol/L) caused a modest dissociation (10-30%) of the renin inhibitors from plasma proteins at both pH values; and the effects of both proteinase inhibitors together were similar to those of 8-hydroxyquinoline alone. At pH 7.4, phenylmethylsulfonyl fluoride increased the potencies of the three renin inhibitors slightly (&lt; or = 43%), whereas IC50 values determined in the presence of 8-hydroxyquinoline decreased by 1.5- to 3.7-fold. The greatest increase in potency occurred with the most hydrophilic compound, and with both angiotensinase inhibitors the effect was no greater than that of 8-hydroxyquinoline alone. The results show that any dissociation of the hypotensive activity measured in vivo from the plasma renin activity measured in vitro is not simply an artifact in the plasma renin activity assay stemming from the use of these angiotensinase inhibitors, especially if only phenylmethylsulfonyl fluoride is used.

Effect of tolbutamide on plasma renin activity.

1979 ◽  
Vol 236 (1) ◽  
pp. E1
Author(s):  
N K Sherma ◽  
V V Gossain ◽  
A M Michelakis ◽  
D R Rovner
Keyword(s):  
Cyclic Amp ◽  
Plasma Renin Activity ◽  
Biological Significance ◽  
Plasma Renin ◽  
Renin Activity ◽  
Control Group ◽  
Cortical Slices ◽  
Intact Rats

The effect of tolbutamide on renin secretion in rats was studied in vivo, and in vitro. Administration of tolbutamide in doses of 12.5 and 25 mg/kg body wt ip to two groups of rats produced no significant change in plasma renin activity compared to the control group. In the in vitro experiments renal cortical slices were incubated with increasing concentrations of tolbutamide (0--4 mg/ml). No significant increase in the net renin production was observed, whereas the concentration of cyclic AMP increased significantly in the incubation medium. These findings suggest that in the intact rats tolbutamide does not increase plasma renin activity. In the renal cortical experiments although tolbutamide increased cyclic AMP production, the increase may not have been sufficient to stimulate the net renin production. These results are of biological significance because of the possible effects of tolbutamide and increased plasma renin activity on the cardiovascular system.

Control of Renin Secretion in Vivo and in Vitro in Rats: Arguments in Favour of a Precursor Form of Renin and of a Role of a Microtubular System

1976 ◽  
Vol 51 (s3) ◽  
pp. 93s-95s ◽  
Author(s):  
F. Banichahi ◽  
A. Capponi ◽  
C. Pricam ◽  
C. De Senarclens ◽  
M. B. Vallotton
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Juxtaglomerular Apparatus ◽  
Granular Endoplasmic Reticulum ◽  
Renin Activity ◽  
Renin Substrate ◽  
Salt Depletion

1. The morphology of the juxtaglomerular apparatus, plasma renin activity, plasma renin substrate and renal renin have been studied in rats after maximal stimulation by bilateral adrenalectomy and salt depletion, and also after blocking this stimulation by deoxycorticosterone and salt load. 2. After stimulation the juxtaglomerular apparatus showed a well-developed granular endoplasmic reticulum and a low secretory granule content. Plasma renin activity was markedly elevated and plasma renin substrate was low. After blockade numerous specific granules with crystalline structures were seen and the granular endoplasmic reticulum was less developed. Plasma renin activity was now low and plasma renin substrate elevated. 3. After prior acidification of the kidney extract a significant increase of renal renin was observed in both conditions but was greater in the second group at the time when large numbers of young granules containing crystalline material were seen. 4. Kidney slices from the adrenalectomized salt-depleted rats released more renin than control slices. Vincristine did not affect this release, but inhibited release from slices stimulated by isoprenaline.

Renal perfusion pressure and renin secretion in the rainbow trout, Salmo gairdneri

1981 ◽  
Vol 59 (7) ◽  
pp. 1220-1226 ◽  
Author(s):  
J. R. Bailey ◽  
D. J. Randall
Keyword(s):  
Plasma Renin Activity ◽  
Perfusion Pressure ◽  
Plasma Renin ◽  
Renal Perfusion ◽  
Renin Secretion ◽  
Renin Activity ◽  
Renin Release ◽  
Salmo Gairdneri ◽  
Renal Perfusion Pressure

In the trout, Salmo gairdneri, a significant correlation between the amount of blood loss and plasma renin activity was established. This increase in plasma renin activity could be due to stimulation of an intrarenal receptor, thus an isolated nonfiltering perfused kidney preparation was developed to test this hypothesis. It was found that a decrease in renal perfusion pressure resulted in an increase in renin release (as measured by perfusate renin activity) but an increase in renal perfusion pressure had no effect on renin release. The increase in renin secretion in response to a decreased renal perfusion pressure was not affected by sympathetic nervous system blocking agents, whereas angiotensin II will apparently inhibit renin secretion in vitro. It was concluded that a baroreceptor response, similar to that found in mammals, is found in fishes and a model mechanism for renin secretion in fishes is proposed.

Effects of indomethacin on plasma renin activity in the conscious rat

1981 ◽  
Vol 240 (3) ◽  
pp. E286-E289 ◽  
Author(s):  
S. Suzuki ◽  
R. Franco-Saenz ◽  
S. Y. Tan ◽  
P. J. Mulrow
Keyword(s):  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Renin Activity ◽  
Renin Release ◽  
Sodium Retention ◽  
Conscious Rat ◽  
Basal Plasma ◽  
Inhibition Of Prostaglandin Synthesis

The role of prostaglandins in the control of renin release in vivo was evaluated in the conscious rat. Indomethacin suppressed urinary prostaglandin E2 (PGE2) excretion from 5.3 +/- 0.5 to 2.6 +/- 0.5 ng/3 h (P less than 0.001). Basal plasma renin activity (PRA) fell from 6.20 +/- 1.07 to 2.98 +/- 0.45 ng . ml-1 . h-1 (P less than 0.02). Indomethacin suppressed PRA stimulated by furosemide, insulin-induced hypoglycemia, hydralazine, isoproterenol, arachidonic acid, and sodium-free diet, whereas PRA stimulated by PGE2 was not suppressed by indomethacin. The suppression of PRA by indomethacin in the sodium-deplete state rules out sodium retention as the mechanism of action of indomethacin. These results indicate that inhibition of prostaglandin synthesis by indomethacin partially blocks the renin response to several of the known stimulators, suggesting that prostaglandins may play a pivotal role in the control of renin release.

Regional renin release by the cat kidney in vitro and in vivo

1979 ◽  
Vol 237 (3) ◽  
pp. F188-F195
Author(s):  
S. M. Jones ◽  
J. Torretti ◽  
J. S. Williams ◽  
S. F. Weinberger
Keyword(s):  
Flow Distribution ◽  
Plasma Renin ◽  
Venous Drainage ◽  
Renin Release ◽  
Kidney Cortex ◽  
Angiotensin I ◽  
Outer Cortex ◽  
Fresh Tissue

Differences in the rate of renin release by superficial and deep areas of the cat kidney cortex were studied in vitro and in vivo. Renin release in vitro by outer cortical slices was significantly higher than by their inner counterparts: 19.6 +/- 2.3 vs. 12.8 +/- 1.95 ng angiotensin I-h-1-mg fresh tissue-1-h of incubation-1. In vivo blood was sampled from subcapsular (outer cortical) and deep (inner cortical and medullary) renal venous circulation from anesthetized cats. Renal venous minus arterial plasma renin concentration was respectively, 4.3 +/- 1.12 and 1.9 +/- 1.04 ng angiotensin I-ml-1-h-1 (P less than 0.01). By assuming that in these experiments renal blood flow distribution was approximately equal to each of the two areas of venous drainage, as reported in the isolated perfused cat kidney, we infer from the regional differences in arteriovenous concentration that the rate of renin release of the outer cortex is higher than that of the innder cortex in the cat kidney in vivo. Tissue content of renin was found to decrease toward the deep cortex. The results support the concept that the rate of regional renin release correlates with tissue renin content, at least under the conditions of the present experiments.

scholarly journals A fluorogenic near-infrared imaging agent for quantifying plasma and local tissue renin activity in vivo and ex vivo

2012 ◽  
Vol 303 (4) ◽  
pp. F593-F603 ◽  
Author(s):  
Jun Zhang ◽  
Dorin V. Preda ◽  
Kristine O. Vasquez ◽  
Jeff Morin ◽  
Jeannine Delaney ◽  
...  
Keyword(s):  
Plasma Renin Activity ◽  
Near Infrared ◽  
Ex Vivo ◽  
Kidney Tissue ◽  
Plasma Renin ◽  
Renin Activity ◽  
Imaging Agent ◽  
Ang Ii

The renin-angiotensin system (RAS) is well studied for its regulation of blood pressure and fluid homeostasis, as well as for increased activity associated with a variety of diseases and conditions, including cardiovascular disease, diabetes, and kidney disease. The enzyme renin cleaves angiotensinogen to form angiotensin I (ANG I), which is further cleaved by angiotensin-converting enzyme to produce ANG II. Although ANG II is the main effector molecule of the RAS, renin is the rate-limiting enzyme, thus playing a pivotal role in regulating RAS activity in hypertension and organ injury processes. Our objective was to develop a near-infrared fluorescent (NIRF) renin-imaging agent for noninvasive in vivo detection of renin activity as a measure of tissue RAS and in vitro plasma renin activity. We synthesized a renin-activatable agent, ReninSense 680 FAST (ReninSense), using a NIRF-quenched substrate derived from angiotensinogen that is cleaved specifically by purified mouse and rat renin enzymes to generate a fluorescent signal. This agent was assessed in vitro, in vivo, and ex vivo to detect and quantify increases in plasma and kidney renin activity in sodium-sensitive inbred C57BL/6 mice maintained on a low dietary sodium and diuretic regimen. Noninvasive in vivo fluorescence molecular tomographic imaging of the ReninSense signal in the kidney detected increased renin activity in the kidneys of hyperreninemic C57BL/6 mice. The agent also effectively detected renin activity in ex vivo kidneys, kidney tissue sections, and plasma samples. This approach could provide a new tool for assessing disorders linked to altered tissue and plasma renin activity and to monitor the efficacy of therapeutic treatments.

Enhancement of the Antihypertensive Effect of Hydrochlorothiazide in Dogs after Suppression of Renin Release by Beta-Adrenergic Blockade

1975 ◽  
Vol 48 (2) ◽  
pp. 147-151
Author(s):  
C. S. Sweet ◽  
M. Mandradjieff
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Arterial Blood Pressure ◽  
Antihypertensive Effect ◽  
Plasma Renin ◽  
Renin Activity ◽  
Renin Release ◽  
Antihypertensive Activity ◽  
Adrenergic Blockade ◽  
Arterial Blood

1. Renal hypertensive dogs were treated with hydrochlorothiazide (8−2 μmol/kg or 33 μmol/kg daily for 7 days), or timolol (4.6 μmol/kg daily for 4 days), a potent β-adrenergic blocking agent, or combinations of these drugs). Changes in mean arterial blood pressure and plasma renin activity were measured over the treatment period. 2. Neither drug significantly lowered arterial blood pressure when administered alone. Plasma renin activity, which did not change during treatment with timolol, was substantially elevated during treatment with hydrochlorothiazide. 3. When timolol was administered concomitantly with hydrochlorothiazide, plasma renin activity was suppressed and blood pressure was significantly lowered. 4. These observations suggest that compensatory activation of the renin-angiotensin system limits the antihypertensive activity of hydrochlorothiazide in renal hypertensive dogs and suppression of diuretic-induced renin release by timolol unmasks the antihypertensive effect of the diuretic.

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