Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of nitric oxide in renal function has been assessed with pharmacologic and physiologic interventions. Pharmacologically, the renal vasodilation and, to some extent, the natriuresis produced by endothelium-dependent vasodilators such as acetylcholine and bradykinin are mediated by nitric oxide and also by prostaglandins. However, prostaglandins and nitric oxide do not participate in the renal effects produced by endothelium-independent vasodilators such as atrial natriuretic peptide, prostaglandin I2, and nitroprusside. Physiologically, nitric oxide and prostaglandins exert a strong regulation on the effects produced by changes in renal perfusion pressure. Increments in renal perfusion pressure within the range of RBF autoregulation appear to inhibit prostaglandin synthesis while simultaneously enhancing the formation of nitric oxide. Nitric oxide modulates autoregulatory vasoconstriction and at the same time inhibits renin release. Conversely, a decrease of renal perfusion pressure to the limit of or below RBF autoregulation may inhibit the synthesis of nitric oxide but may trigger the release of prostaglandins, whose vasodilator action ameliorates the fall in RBF and stimulates renin release. Nitric oxide and prostaglandins are also largely responsible for mediating pressure-induced natriuresis. However, unlike prostaglandins, mild impairment of the synthesis of nitric oxide in systemic circulation produces a sustained decrease in sodium excretion, which renders blood pressure susceptible to be increased during high-sodium intake. This effect suggests that a deficiency in the synthesis of nitric oxide could constitute the most effective single disturbance to foster the development of a syndrome similar to that seen in salt-sensitive hypertension.
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PMID:Role of the endothelium-dependent relaxing factor nitric oxide on renal function. 162 61

Although endothelium-derived prostaglandin I2 stimulates renin release, exogenous endothelium-derived relaxing factor (EDRF) can inhibit it. To characterize the role of EDRF as an endogenous regulator of renin release, we inhibited or stimulated its production in rat renal cortical slices in vitro. Renin concentration in the incubation medium was determined by radioimmunoassay for angiotensin I (Ang I) generation. NG-Monomethyl-L-arginine (LNMMA) (10(-4) M), which blocks EDRF formation, significantly enhanced basal renin release from kidney slices by more than 50% in control medium (40.0 +/- 14.3 ng Ang I/hr/mg/30 min; p less than 0.01) or in medium treated with 1.6 x 10(-5) M meclofenamate (50.8 +/- 8.4 ng Ang I; p less than 0.025). Isoproterenol (10(-5) M)-stimulated renin release (40.0 +/- 14.3 ng Ang I; p less than 0.02) was not modified by LNMMA; addition of L-arginine (10(-5) M), the precursor of EDRF, did not change basal but blocked isoproterenol stimulation of renin. Nitroprusside (10(-5) M) completely reversed melittin-stimulated renin release. Endothelin-1, an endothelium-derived vasoconstrictor, inhibits renin release and stimulates EDRF and prostaglandin synthesis. To determine whether any of the renin-inhibiting effect of endothelin-1 was due to its stimulation of EDRF, we compared the effect of endothelin-1 on cortical slices with and without EDRF inhibition. Endothelin-1 (10(-7) M) decreased renin by 36.7 +/- 10.9 ng Ang I (p less than 0.01) compared with controls, and the response was the same after either LNMMA or hemoglobin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nonprostanoid endothelium-derived factors inhibit renin release. 173 97

The effects of specific renin inhibitors, angiotensin converting enzyme inhibitors, indomethacin, and prostaglandin I2 analogue on the release of angiotensins from isolated and Krebs-Ringer-perfused rabbit mesenteric arteries were examined. Three different renin inhibitors suppressed release of angiotensins in dose-dependent manners. At the highest concentration (10(-7) M), the inhibitors EMD 52,620, EMD 54,388, and EMD 52,742 induced 46%, 52%, and 48% decreases, respectively, in the basal rate of immunoreactive angiotensin II release. These results provide clear evidence that released angiotensins are produced by the specific action of vascular renin and that the renin inhibitors suppress the vascular renin-angiotensin system as well as the circulating renin-angiotensin system and appear to provide a useful mode for the treatment of hypertension. Nonsulfhydryl angiotensin converting enzyme inhibitors cilazapril and delapril were more effective than captopril, and ramipril was equipotent to captopril, suggesting that the effectiveness of angiotensin converting enzyme inhibitors on the vascular renin-angiotensin system cannot be explained only by its inhibitory effect on angiotensin converting enzyme. Indomethacin, which was reported to suppress angiotensin II release from rat hind limbs, elicited a dose-dependent increase of angiotensin release from rabbit mesenteric arteries. These results suggest that a difference exists in the regulatory mechanisms in the release of angiotensins from diverse vascular beds.
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PMID:Significance of vascular renin for local generation of angiotensins. 199 57

In our previous studies, we showed an in vivo stimulating effect of the extract of the rat submandibular gland on plasma inactive renin release. In this study, we evaluated the effects of the rat submandibular gland extract and of some plasma active renin stimulants on inactive renin release from rat renal cortical slices. Adult male Wistar rats (250-350g) were kept on a regular diet (Na 260mg/100g) and nephrectomized under pentobarbital anesthesia (50mg/kg, i.p.). Five thin renal cortical slices were obtained from each kidney by using a razor blade. These renal cortical slices were incubated in Earle's buffer (pH7.4, Difco) at 37 degrees C for 30 min (preincubation), then transferred into 10ml fresh Earle's buffer with or without some agents and incubated at 37 degrees C for 1 hour (experimental incubation). For each experiment, 6 groups of 5 renal cortical slices were employed. The agents used in this study were as follows: isoproterenol (10(-5)M), furosemide (50 micrograms/ml), prostaglandin E1 (10(-5)M), prostaglandin I2 (10(-5)M) and the rat submandibular gland extract (100 microliters) which was obtained after homogenation with 10 x (w/v) 0.01M pyrophosphate buffer (pH6.5) including 0.1M NaCl. One ml of samples of this Earle's buffer were withdrawn every 20 min. Active renin in the samples was assayed by the commercial RIA-kit (Dainabot), and total renin was assayed after trypsin (Worthington) treatment (30 micrograms/300 microliters sample) at 4 degrees C for 10 min. Inactive renin was determined as the difference between total renin and active renin. Active and inactive renins increased linearly in the buffer without any agents (control) during the observation period (60 min). Isoproterenol (10(-5)M) stimulated the release of active renin significantly (p less than 0.01 vs. control) but did not affect the release of inactive renin. Furosemide (50 micrograms/ml) stimulated the release of active and inactive renins significantly at 20 and 40 min (p less than 0.05 vs. control) but did not affect the release of either renin at 60 min. Both prostaglandins E1 and I2 (10(-5)M) stimulated the release of active renin significantly (p less than 0.01 vs. control) but inhibited, on the other hand, the release of inactive renin significantly (p less than 0.01 vs. control). The rat submandibular gland extract (100 microliters) did not affect the release of active renin but stimulated the release of inactive renin significantly (p less than 0.05 vs. control).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Release mechanisms of inactive renin from rat renal cortical slices: role of the submandibular gland]. 211 63

In our present studies, we evaluated the role of the submandibular glands (SMG) on plasma inactive renin (PIR) releasing mechanisms in rats using some agents which are known to stimulate plasma active renin (PAR) release. The results were analyzed between sialoadenectomized (SX) and sham-operated (control: C) rats. Twenty-four h after the operation, PAR releasing agents, furosemide (FRO) 2.5 mg/rat/h with prior iv bolus 5 mg, captopril (CAP) 5 mg/rat/h with prior iv bolus 10 mg, 1-Sar-8-Ile-angiotensin II (Ang II A) 300 ng/kg/min, prostaglandin E1 (PGE1) 100 ng/kg/min, and prostaglandin I2 (PGI2) 100 ng/kg/min, were infused through femoral venous cannulae. Blood samples were taken through femoral arterial cannulae into test tubes containing 2 mg EDTA-2Na. PAR was assayed by RIA, and total renin was obtained after tryptic activation. According to the responses of PIR, the agents used were categorized into three patterns: FRO increased PIR, both PGs lowered PIR, and, CAP and Ang II A had no effect on PIR release. The PIR release mechanisms by FRO were further investigated by 20 mg FRO ip injection in totally nephrectomized rats. PIR increased even in nephrectomized rats, but the increase was totally canceled by the following SX. In conclusion, FRO alone among some agents studied is able to stimulate PIR release only under the existence of SMG.
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PMID:[Role of the submandibular glands in in vivo mechanisms of plasma inactive renin release in the rat]. 220 Jul 23

1. Changes in tension in response to cumulative additions of angiotensins (i.e., angiotensinogen, angiotensin I and angiotensin II), bradykinin and acetylcholine were monitored isometrically on ring preparations from porcine interlobar renal arteries. 2. Angiotensins consistently elicited contractile responses, whereas both bradykinin and acetylcholine produced relaxation of the arterial rings when active tone was induced by prostaglandin F2 alpha. 3. Contractile responses to angiotensin II could be completely blocked by the combined action of the cyclo-oxygenase inhibitor, indomethacin (1 microM) and the lipoxygenase inhibitor, nordihydroguairetic acid (NDGA, 10 microM). 4. Relaxant responses to bradykinin were unchanged during blockade of thromboxane A2 synthesis by dazoxiben (30 microM) and proved to be largely resistant to blockade by indomethacin (1 microM) and the prostaglandin I2 (prostacyclin) synthesis inhibitor, tranylcypromine (40 microM). 5. The angiotensin receptor blocker, saralasin (10 and 100 nM) antagonized responses to angiotensinogen, angiotensin I and angiotensin II effectively and with similar potency. Enalaprilic acid, the active metabolite of the converting enzyme inhibitor enalapril (300 nM), attenuated responses to angiotensin I but failed to inhibit those to angiotensinogen up to 1 microM. The serine protease kallikrein (0.001 to 1 mu ml-1) produced a dose-dependent shift to the left of the concentration-response curve for angiotensinogen. 6. It is suggested that the porcine interlobar renal artery possesses a local renin-angiotensin system with activatable angiotensin II forming enzyme(s) within the vessel wall.
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PMID:Pharmacological evidence for the existence of a local renin-angiotensin system in porcine interlobar renal arteries. 228 72

Beraprost sodium (sodium (+/-)-(1R*,2R*,3as*,8bS*)-2,3,3a,8b-tetrahydro-2- hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H- cyclopenta[b]benzofuran-5-butyrate, TRK-100) is an orally active epoprostenol (prostaglandin I2, PGI2) analogue. Its general pharmacological effects on peripheral organs were studied. 1. In isolated organs, beraprost sodium relaxed the trachea and increased atrial beating rate (2.4 x 10(-5) mol/l). It also dose-dependently contracted the stomach, aorta, ileum and uterus (2.4 x 10(-7)-2.4 x 10(-4) mol/l). These effects of beraprost sodium were similar, but inferior to those of PGI2 and PGE1. 2. Intravenous administration of beraprost sodium produced a dose-related decrease in blood pressure (BP), its potency being about 1/3 times that of PGI2 in anesthetized rats and dogs. Beraprost sodium and PGI2 had no effects on heart rate (HR), and enhanced respiration in conjugation with a decrease in BP. Oral administration of beraprost sodium in high doses (1-3 mg/kg in rats and 0.3 mg/kg in dogs) caused a decrease in BP. A compensatory tachycardia and an elevated plasma renin activity (PRA) occurred after low doses (0.1-0.3 mg/kg) in rats. In contrast, a change of HR and PRA in rabbits and dogs was mild. 3. Beraprost sodium produced suppression of digestive organs: markedly, gastric motility and secretion and intestinal transport; slightly, but significantly, biliary secretion. On the other hand, it enhanced ileal motility at a high dose (300 micrograms/kg i.v.). 4. Oral administration of beraprost sodium caused a decrease in urinary volume and electrolyte excretion in rats. 5. Oral administration of beraprost sodium prolonged bleeding time in mice, while it had no effect on the blood coagulation system in vitro. In addition, beraprost sodium had no hemolytic action. 6. The other effects of beraprost sodium were weak. Beraprost sodium had no local anesthetic activity and no effect on salivation, pupil size and neuromuscular transmission in the skeletal muscle. Beraprost sodium slightly contracted the uterus of non-pregnant rats in situ and dose-independently inhibited carrageenin-induced paw edema. In conclusion, beraprost sodium produced various effects on the autonomic, cardiovascular, and gastrointestinal systems. Probably, these effects may be based on its own action like PGI2.
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PMID:General pharmacology of beraprost sodium. 2nd communication: effect on the autonomic, cardiovascular and gastrointestinal systems, and other effects. 251 Jul 43

Because pressure-related natriuresis may be central to the regulatory role of the kidney on blood pressure, it is important to understand the relationship of humoral systems involved in the control of renal hemodynamics and tubular function. The preglomerular endothelial synthesis of prostaglandin I2 and endothelium-derived relaxing factor seem to modulate autoregulatory control by the afferent arterioles and the release of renin by the juxtaglomerular apparatus. The release of renin is followed by an increase in angiotensin II in the renal interstitium, which is responsible for adjusting the vascular tone of the efferent arterioles and vasa recta and for stimulating proximal tubular reabsorption of sodium. Variations in medullary circulation induced by angiotensin II could alter medullary interstitial pressure and the medullary production of prostaglandins E2 and I2 and, ultimately, could modulate sodium reabsorption in the medullary thick ascending limbs and the collecting ducts.
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PMID:Intrarenal mechanisms that regulate sodium excretion in relationship to changes in blood pressure. 251 59

Understanding the sequence of events responsible for pressure-related natriuresis and their pathophysiologic alterations may be useful in distinguishing various types of essential hypertension of renal origin. The perturbation of a distal step in the sequence is likely to be reflected in a simple physiologic defect. For instance, pathophysiologic alterations in the medullary production of prostaglandin E2 might directly influence natriuresis and diuresis because of its modulatory effect on tubular reabsorption of sodium and water. Perturbation of more proximal steps in the sequence could influence all the distal events as well. For instance, prostaglandin I2 and endothelium-derived relaxing factor may be produced by the preglomerular vasculature in response to alterations in renal perfusion pressure and may modulate the release of renin from the juxtaglomerular cells. Thus, variations in the production of prostaglandin I2 or endothelium-derived relaxing factor may be reflected by various renal vascular, tubular, and systemic homeostatic events related to the renin-angiotensin system.
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PMID:Alterations in blood pressure by derangement of the mechanisms that regulate sodium excretion. 251 60

Treatment with a converting enzyme inhibitor has been shown to stimulate aortic prostaglandin I2 synthesis. We studied whether converting enzyme inhibitor-stimulated prostaglandin I2 synthesis might be mediated by kinins. Anesthetized male Sprague-Dawley rats were given a continuous 70-minute infusion of either saline or a kinin analogue antagonist, [DArg0-Hyp3-Thi5-DPhe7-Thi8]bradykinin, 8 micrograms/kg/min. After 10 minutes, rats were given an intravenous bolus of either vehicle or the converting enzyme inhibitor enalaprilat (30 micrograms/100 g body wt). After 70 minutes, aorta and renal cortical slices were harvested and incubated in vitro in buffer without drugs at pH 7.4, 37 degrees C for 60 minutes. The buffer was then sampled for measurement of 6-keto prostaglandin F1 alpha (an index of prostaglandin I2), prostaglandin E2, and renin release (angiotensin I generation) by radioimmunoassay. The aortic prostaglandin I2 from rats treated with converting enzyme inhibitor was significantly elevated (36.7 +/- 5.0 ng/mg dry wt/hr) compared with aorta from rats treated with either vehicle (25.6 +/- 2.2 ng/mg/hr), kinin antagonist (25.1 +/- 2.4 ng/mg/hr), or kinin antagonist plus converting enzyme inhibitor (23.0 +/- 2.0 ng/mg/hr), p less than 0.02. There were no differences in aortic prostaglandin E2, renin release, or prostaglandin E2 from renal cortical slices. Direct in vitro incubation of aorta with molar concentrations of converting enzyme inhibitor from 10(-9) to 10(-4) had no effect on prostaglandin I2. These results suggest that kinins may mediate the effect of converting enzyme inhibition on aortic prostaglandin I2 synthesis and thereby may account for part of the hemodynamic responses resulting from treatment using converting enzyme inhibitors.
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PMID:Kinin antagonist reverses converting enzyme inhibitor-stimulated vascular prostaglandin I2 synthesis. 254 21


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