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 purpose of the study was to evaluate the antihypertensive effect of enalapril administered once daily (q.d.), and to assess the effectiveness of enalapril in achieving sustained blockade of the renin-angiotensin system. The study population comprised 15 patients with uncomplicated, moderate essential hypertension whose blood pressure (BP) was not adequately controlled on hydrochlorothiazide (HCTZ) monotherapy. Enalapril 10-40 mg q.d. produced a significant fall in supine and erect BP (24 h after enalapril) that persisted during 1 year of combination therapy with HCTZ and enalapril. Blood pressure 6 h after enalapril was significantly lower than BP measured 24 h after enalapril, and occasionally at hypotensive levels. Plasma angiotensin II concentration fell significantly after enalapril with reciprocal increases in the plasma concentrations of renin and angiotensin I. The blockade of the renin-angiotensin system was maintained throughout the study. Bradykinin could not be detected in venous blood at any time during the study. We conclude that combination therapy with HCTZ and enalapril once daily is a rational, simple, and effective treatment in patients with moderate essential hypertension.
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PMID:One year antihypertensive treatment with enalapril once daily: clinical and biochemical effects. 248 57

Smooth muscle cells were cultured from an arteriole-rich fraction of the rabbit renal cortex and characterized by their ultrastructural and immunohistochemical features, their high content in creatine kinase (60-times that of the initial preparation) and their ability to synthesize renin. Cells, studied between passages 2 and 5, produced mainly PGE2 and, to a lesser extent, PGF2 alpha. Bradykinin (BK) (0.1 nM-1 microM) induced a concentration-dependent increase in PGE2 (28-40-times basal value at 1 microM after a 5 min incubation period) and stimulated also the free cytosolic calcium concentration [( Ca2+]i) with a 2-fold maximal rise to its basal value. Both effects, inhibited by the anti-B2 receptor [Thi5.8D-Phe7] BK, were not reproduced by DesArg9 BK. A decrease in the extracellular calcium concentration and incubation in the presence of a calcium-channel blocker (lanthanum chloride) inhibited the BK-dependent rise of [Ca2+]i but not that of PGE2. Preincubation with phorbol myristate acetate increased basal and BK-induced PGE2 synthesis but prevented the effect of BK on [Ca2+]i. These results demonstrate the ability of BK to increase [Ca2+]i and PGE2 production in cultured vascular cells from the rabbit renal cortex and suggest that kinins might act on the cortical microcirculation via their direct effects on arteriolar smooth muscle cells.
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PMID:Effects of bradykinin on prostaglandin synthesis and cytosolic calcium in rabbit subcultured renal cortical smooth muscle cells. 257 Jun 9

Numerous studies have suggested that a functional relationship exists between the renal kallikrein-kinin and renin-angiotensin systems. We used an in vitro preparation of isolated glomeruli to study the effect of kinins on renin release. Glomeruli were harvested from the dissected cortices of rat kidneys by a passive sieving technique. They were then placed in chambers and superfused with aerated modified Krebs buffer, and the chamber effluent was collected during two sequential 10-min periods. Bradykinin at 10(-6) M increased renin release from 2.17 +/- 0.34 to 4.05 +/- 0.72 ng ANG I/min, and 10(-5) M bradykinin increased renin release from 3.51 +/- 0.64 to 8.94 +/- 1.27 ng ANG I/min. With albumin-modified buffer, 10(-5) M bradykinin stimulated renin release from 7.11 +/- 0.79 to 14.03 +/- 2.36 ng/min. Lys-bradykinin at 10(-5) M also increased renin release from 5.69 +/- 1.11 to 14.50 +/- 2.65 ng ANG I/min. However, neither of the inactive kinin analogues, [Tyr8]bradykinin or des-Arg9-bradykinin, had any effect on renin release. We found that isolated glomeruli were relatively free of kininase activity, in contrast to the high activity found in the kidney slice preparation or in rat plasma. These results suggest that biologically active kinins can stimulate renin release in an in vitro preparation that is free of degradative kininases and independent of hemodynamic and neural influences.
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PMID:Kinin stimulation of renin release in isolated rat glomeruli. 298 45

Extensive research has focused on the mechanisms by which converting enzyme inhibitors, such as captopril, lower the systemic blood pressure. In addition to inhibiting the conversion of angiotensin I to angiotensin II, these agents have been proposed to influence other systems which might affect vascular resistance including the kinins and the prostanoids. This study was designed to evaluate whether captopril has any direct effect to increase the synthesis of endogenous vasodilator prostanoids in either freshly isolated rabbit renal preglomerular microvessels or in endothelial cells derived from them. The results indicate that captopril, in a variety of doses, had no effect on the synthesis of either prostacyclin or PGE2 by renal preglomerular microvessels. Bradykinin, on the other hand, increased prostanoid production significantly in the same tissue preparations. Finally, captopril had no effect in altering bradykinin-induced increases in renovascular prostanoid biosynthesis. Thus, captopril appears to have no ability to enhance the production of vasodilator prostanoids in rabbit renal preglomerular resistance vessels. These data question the role of prostanoid-related mechanisms in the non-renin-related antihypertensive actions of captopril.
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PMID:Lack of effect of captopril on preglomerular renal microvascular prostanoid biosynthesis. 328 53

Bradykinin can increase prostaglandin synthesis and also stimulate renin release in vitro. Because prostaglandins also stimulate renin, studies were performed to determine whether bradykinin stimulation of renin is a function of prostaglandin synthesis. Isolated glomeruli with attendant arteriolar attachments were harvested from rat kidneys and superfused. The effluent was analyzed for renin, prostaglandins E2 and I2 (6-keto-PGF1 alpha). Bradykinin (10(-5) M) increased renin by 50% with a concomitant increase in prostacyclin (PGI2) but not in prostaglandin E2 (PGE2). The cyclooxygenase inhibitor meclofenamate (1.6 X 10(-5) M) inhibited bradykinin-induced PGI2 synthesis but not the concurrent increase in renin release. Additionally, neither the phospholipase inhibitor quinacrine (10(-2) M) nor the prostacyclin synthetase inhibitor 9,11-azoprosta-5,13-dienoic acid (Azo analogue-1) (5.67 X 10(-6) M) eliminated bradykinin-induced renin release. Superfusion with calcium-free media and EDTA increased basal renin release 2.5-fold, and bradykinin stimulated a twofold increase in renin release. Neither a high (10(-2) M) media calcium nor the calcium channel blocker nifedipine (10(-6) M) eliminated bradykinin stimulation of renin. These results suggest that bradykinin stimulation of renin is at least partially independent of prostaglandin synthesis and that bradykinin must act by some prostaglandin-independent pathway to induce renin release from isolated glomeruli.
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PMID:Prostaglandin independence of kinin-stimulated renin release. 355 16

1. When applied directly to the brain, angiotensin II amide, as either the valine(5) octapeptide, causes rats in normal fluid balance to drink water.2. The drinking response to angiotensin injections is copious, rapid, repeatable within the same test session, and stable over months of testing in the same animal.3. The response is motivationally potent and specific. After injection the animals move directly to the source of water and drink. There is typically no preliminary hyperactivity or subsequent depression. The animals do not eat, gnaw or exhibit other behaviours that are not normally seen during spontaneous drinking. The injections rouse sleeping animals to drink and interrupt eating in animals deprived of food for two days.4. The region of the brain that is most sensitive to angiotensin includes the anterior hypothalamus, the preoptic region, and the septum including the nucleus accumbens.5. Intracranial renin elicited drinking. Bradykinin and vasopressin did not, nor did adrenaline, noradrenaline or aldosterone. In the most sensitive region, sites positive for angiotensin also yielded drinking to carbachol.6. Responses were obtained with 5 ng (ca. 5 p-mole) and occurred reliably with 50 ng angiotensin or more. The dose-response curve for amount drunk rose from 5 to 100 ng and levelled off thereafter. Angiotensin is therefore the most potent dipsogen known and is effective at doses that are reasonably within the concentration range for circulating endogenous angiotensin.7. Injections into the sensitive region of doses of angiotensin that were effective for drinking did not produce peripheral haemodynamic changes in lightly anaesthetized rats.8. This work strengthens the suggestion that angiotensin is a natural hormone of drinking behaviour that participates in extracellular thirst by its release from the kidney and subsequent direct action on a specific chemoreceptive region in the anterior diencephalon and limbic lobe.
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PMID:Drinking induced by injection of angiotensin into the rain of the rat. 432 23

Polypeptides are endogenous agents, involved in the regulation of many physiologic functions and the pathogenesis of several diseases. Polypeptide antagonists form a group of new chemical entities which may provide valid therapeutic agents. Some polypeptides (angiotensin, kinins) are released through the action of proteolytic enzymes (renin, kallikreins) and act as hormones or autacoids; others (substance P, neurotensin) are synthetized by nervous cells to serve as neurotransmitters or neuromodulators. The main homeostatic role of the renin-angiotensin system is to uphold high systemic arterial blood pressure. Overproduction of renin and insufficient checking of renin secretion are among the most common causes of arterial hypertension. Several forms of arterial hypertension (neurovascular, idiopathic) benefit from a reduction in renin-angiotensin system activity. This is achieved either through decreasing renin secretion, by inhibiting conversion of angiotensin I into angiotensin II, or through blocking the peripheral actions (at the receptor sites) of angiotensin II. Renin secretion is very significantly reduced by beta-blocking agents (propranolol); conversion of angiotensin I into angiotensin II is inhibited by teprotide, captopril and their derivatives; peripheral actions of angiotensin II are blocked by saralasin. Bradykinin and related agents produce vasodilation, increase vascular permeability and stimulate pain fibers. Kinins thus reproduce the cardinal features of inflammation and are held to be mediators of the inflammatory reaction. The substance P neuropeptide is found in the brain and bowel; it may act as a transmitter of the sensation of pain at the spinal cord and central nervous system sites. Among other effects outside of the brain, substance P is a potent vasodilator and inhibits renin secretion. Neurotensin is a neuropeptide which produces hypothermia, muscular relaxation and analgesia. Outside of the brain, this peptide is involved in the regulation of gastric secretion, intestinal motility and insulin and glucagon secretion. The vasoactive intestinal peptide, found in certain cholinergic nerve endings, is a large peptide which inhibits gastric secretion, intestinal motility and vascular tone.
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PMID:[Polypeptides and antagonists]. 620 6

Both inactive and active renin were released from renal cortical slices of the hog. Isoproterenol, prostaglandin E1, and dibutyryl cAMP stimulated the release of both inactive and active renin. Renal kallikrein caused selective stimulation of the release of active renin and suppressed the release of inactive renin. Bradykinin and kallidin did not stimulate renin release. The effect of kallikrein was abolished by aprotinin but not by indomethacin. These observations indicate that the effect of kallikrein is not mediated via kinin formation or prostaglandin generation. The data suggest that there may be at least two types of mechanism for renin release from hog kidney. One is of the nonselective type by which both active and inactive renin are released, as in the case of beta-adrenergic or prostaglandin stimulation. The other is a selective mechanism by which only active renin is preferentially released, as in the case of urinary or renal kallikrein stimulation.
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PMID:Release of active and inactive renin from hog renal cortical slices in vitro. 620 37

Captopril, an inhibitor of angiotensin converting enzyme, was administered twice daily to 13 hypertensive patients for a mean period of 9 weeks. Continuous blood pressure control in the ambulatory patients was established with a portable blood pressure recorder. Notwithstanding, in eight patients with normal renal function, plasma converting enzyme was found to resume normal activity before administration of the morning dose of captopril. Only in 5 patients with impaired renal function did some blockade of plasma converting enzyme persist for more than 12 hours. Measured plasma converting enzyme activity seemed to reflect total conversion of angiotensin I, including conversion in the pulmonary vascular bed, since changes in its activity were closely paralled by changes in plasma aldosterone levels. Bradykinin accumulation seems unlikely when converting enzyme and thus, presumably, kininase II has resumed normal activity. Captopril administration does not seem to alter plasma epinephrine or norepinephrine levels. Blood pressure reduction in the face of normal angiotensin converting enzyme activity is probably due to hyporesponsiveness of the arterioles to pressor hormones, which may be due to specific renin-related and/or nonspecific effects of captopril.
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PMID:Discrepancy between antihypertensive effect and angiotensin converting enzyme inhibition by captopril. 624 69

Bradykinin (BK) and [des-Arg9]-bradykinin (-9BK) concentrations in blood and urine samples from 18 normotensive subjects and 23 patients with low-renin essential hypertension were determined by radioimmunoassay. BK and -9BK levels in venous blood from normotensive subjects were 67.1 +/- 60.8 pg/ml and 204.1 +/- 44.5 (mean +/- S.D.), respectively, and levels in urine from normotensive subjects were 5.3 +/- 5.3 ng/ml and 1.6 +/- 1.2, respectively. The blood and urinary levels of BK and -9BK in low-renin essential hypertensives were not significantly different from those of normotensives and did not change when the hypertensives were treated with the new orally active angiotensin I-converting enzyme (ACE) inhibitor, enalapril (MK421). It has been proposed that BK levels do not change with ACE inhibition because under these conditions BK might be metabolized to -9BK by kininase I. Since -9BK levels did not increase with MK421 treatment, this possibility can be excluded. The absence of elevations in blood and urine BK and -9BK after administration of MK421 does not support an involvement of kinins in the mechanism of antihypertensive action of MK421 in these patients. On the basis of the data, it is not possible to exclude such an involvement, however, because local changes in kinin concentrations could occur that are not reflected by changes in circulating or urinary kinin levels.
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PMID:Immunoreactive bradykinin and [des-Arg9]-bradykinin in low-renin essential hypertension--before and after treatment with enalapril (MK 421). 631 33


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