Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On the rabbit isolated aorta, dose-dependent contractions to both angiotensin II and heptapeptide ([des-Asp1]-angiotensin II) were obtained. The curves were parallel, and reached the same maximum level. On the rat isolated uterus, angiotensin II and the heptapeptide displayed non-parallel dose-response curves. Results obtained with angiotensin-analog antagonists and cross-tachyphylaxis experiments suggest that the heptapeptide and angiotensin II act, preferentially, on different populations of receptors in the uterus. The difference in action of indomethacin on recovery from tachyphylaxis to angiotensin II and heptapeptide on rat isolated aorta suggests that the mechanism of induction of tachyphylaxis by these two peptides may differ. SQ 20881, the angiotensin converting enzyme inhibitor, totally inhibited uterine responses to both decapeptide and nonapeptide, while slightly potentiating those to angiotensin II and heptapaptide. Indomethacin had no significant effect on uterine responses to either angiotensin II or the heptapeptide.
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PMID:A comparison of the effects of angiotensin II and heptapeptide on smooth muscle (vascular and uterine). 18 63

Bradykinin or prostaglandin E2 (PGE2), when injected intravenously, decreased blood pressure of conscious rats in a dose-dependent manner, while intracerebroventricular injections of bradykinin or PGE2 caused a dose-dependent increase in blood pressure. SQ 14,225, an inhibitor of angiotensin converting enzyme, potentiated the central pressor or peripheral depressor effect of bradykinin. Indomethacin, an inhibitor of prostaglandin synthesis, almost completely inhibited the central pressor effect of bradykinin when injected intraventricularly. Indomenthacin, when injected intravenously, failed to inhibit the peripheral depressor effect of bradykinin, whereas it significantly attenuated the peripheral depressor effect of bradykinin when the angiotensin converting enzyme was inhibited with SQ 14,225. These results suggest that the central pressor effect of bradykinin is mainly mediated by the synthesis of prostaglandins in the central nervous system, while only a small fraction of peripheral depressor effect of bradykinin is, at least in conscious rats, mediated by the synthesis of prostaglandins in the systemic circulation.
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PMID:Central and peripheral effects of bradykinin and prostaglandin E2 on blood pressure in conscious rats. 38 42

Prostaglandins (PG) have been suggested to play a role in the genesis of cough induced by angiotensin-converting enzyme inhibitors (ACE-I) and that inhibition of PG synthesis can reduce or abolish the incidence of this side effect. Moreover, experimental and clinical data suggest that nifedipine, a dihydropyridine Ca antagonist, can inhibit PG synthesis. Therefore, we wished to determine whether nifedipine can reduce cough induced by ACE-I as compared with indomethacin, a known inhibitor of PG synthesis. Fourteen hypertensive patients who developed cough during captopril chronic therapy randomly received slow-release nifedipine 20 mg twice daily (b.i.d.), indomethacin 50 mg b.i.d., and placebo b.i.d. for 1 week in a double-blind, cross-over design. At the end of each treatment phase, cough was evaluated by a self-administered questionnaire containing an ordinal scale for daily cough intensity and frequency. Indomethacin abolished or markedly reduced cough induced by ACE-I, whereas nifedipine reduced it but to a lesser degree. These findings suggest that PG can play a role in cough caused by ACE-I, and a dihydropyridine Ca antagonist can reduce the occurrence of this side effect.
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PMID:Effects of nifedipine and indomethacin on cough induced by angiotensin-converting enzyme inhibitors: a double-blind, randomized, cross-over study. 138 63

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

Incubation of cultured bovine pulmonary artery endothelial cells with 200 microM of 3-isobutyl-1-methylxanthine (IBMX) for 24 hr produced a five- to tenfold increase in cellular angiotensin converting enzyme activity (ACE) above that of untreated control cells. A lesser increase was observed in medium ACE. Other methylxanthines produced a similar, but less marked, effect. The elevation of ACE seemed to require de novo protein synthesis since it was reduced by 0.1 microgram/ml cycloheximide. Elevation of cellular cAMP was detected at 30 min after introduction of IBMX, then rapidly returned to control levels at 1 hour, while elevation in cellular ACE at 24 hr required contact with IBMX for at least 2 hr. Hence, the transient elevation in cAMP is unlikely to be the cause of the elevation of ACE. Phorbol ester and synthetic diacyl glycerol OAG, activators of protein kinase C, did not elevate ACE. Indomethacin, at a concentration known to inhibit cyclooxygenase activity, had no effect on the elevation of ACE. The elevation of ACE by IBMX was not affected by the calcium channel blocker verapamil or the calcium chelator EGTA. In contrast, the effect of IBMX was totally abolished by the calmodulin inhibitors trifluoperazine and calmidazolium. The data show that IBMX elevates endothelial cell ACE and suggest that the elevation is mediated by a calcium-calmodulin complex. The studies demonstrate a novel effect of methylxanthines on endothelial cells in culture.
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PMID:Elevation of angiotensin converting enzyme by 3-isobutyl-1-methylxanthine in cultured endothelial cells: a possible role for calmodulin. 245 40

A variety of kinin peptides, agonists and antagonists were tested with dog carotid and renal arteries in order to characterize kinin receptor types and functions. The dog carotid artery responds to bradykinin with concentration-dependent relaxation only when the endothelium is intact but des-Arg9-bradykinin is practically inactive. The effect of bradykinin is blocked by B2 receptor antagonists, suggesting that the dog carotid artery has B2 receptors in the endothelium. These receptors mediate relaxation of the arterial smooth muscles by promoting the release of an endothelium-derived relaxing factor whose action is prevented by methylene blue. Kinins relax the dog renal artery with or without endothelium. Methylene blue prevents the effect of bradykinin only, suggesting that B2 receptors, promoting the release of endothelium-derived relaxing factor, are present in the endothelium of the dog renal artery. Moreover, the dog renal artery appears to have both B2 and B1 receptors mediating relaxation of the arterial smooth muscle. The presence of the two receptor types has been demonstrated by means of specific agonists and antagonists. Indomethacin blocks the effects of both bradykinin and des-Arg9-bradykinin on the dog renal artery without endothelium, suggesting that muscular B1 and B2 receptors act by promoting the release of prostaglandins. Captopril, a kininase II inhibitor, potentiates the effect of bradykinin on the dog carotid artery more than on the dog renal artery.
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PMID:Receptors for kinins in isolated arterial vessels of dogs. 254 57

The angiotensin converting enzyme inhibitors potentiate the wheal response to intradermal bradykinin. Both converting enzyme inhibitors and bradykinin stimulate prostaglandin synthesis and prostaglandins enhance the cutaneous response to bradykinin. We examined the possibility that the increased wheal response to intradermal bradykinin in the presence of enalapril was due to the effect of prostaglandins. Indomethacin did not inhibit the potentiation by enalapril of the wheal response to bradykinin.
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PMID:The effect of indomethacin and enalapril on the cutaneous response to bradykinin. 254 11

In this study eight healthy volunteers were involved in a randomized, cross-over trial in which they were treated with either 25 mg of captopril b.i.d. or 20 mg of enalapril o.i.d. alone or in combination with 50 mg of indomethacin b.i.d. in order to detect a difference between both converting enzyme inhibitors when interacting with indomethacin. Before and after each 4-d treatment period, blood pressure (determined by random zero sphygmomanometer), body weight, plasma renin activity, angiotensin converting enzyme, plasma potassium, serum creatinine and the 24-h urinary excretion of 6-keto-prostaglandin F1 alpha were measured. Indomethacin attenuated the decrease of supine diastolic blood pressure during treatment with captopril, but not with enalapril. However, the initial decrease of blood pressure on captopril was greater than on enalapril. Both converting enzyme inhibitors had no effect on the urinary excretion of 6-keto-prostaglandin F1 alpha, while indomethacin reduced it. The results suggest a difference between captopril and enalapril in interaction with indomethacin.
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PMID:The interaction between indomethacin and captopril or enalapril in healthy volunteers. 255 88

Nonsteroidal anti-inflammatory drugs like indomethacin and angiotensin converting enzyme inhibitors like captopril have contrasting effects on compensatory changes in glomerular filtration rate and renal blood flow following partial nephrectomy. Conjoint treatment has been little studied. Effects of 7 days of treatment with captopril, indomethacin, or captopril + indomethacin in drinking water were studied in 50% nephrectomized Sprague-Dawley rats. Urinary protein excretion, glomerular filtration rate, effective renal plasma flow (ERPF), mean arterial pressure, renal vascular resistance, and remnant kidney weight were measured. Renal clearance studies were performed using a double-isotope, single-injection method, in conscious rats infused with either saline or saline + prostaglandin E1. Indomethacin induced significant (p less than 0.05) increases in renal vascular resistance (RVR) which were attenuated by either concurrent treatment with captopril or infusion of PGE1 at the time of study. Compensatory growth of the remnant kidney appeared not to be dependent on increments in renal blood flow; captopril decreased RVR and increased ERPF but had no effect on kidney weight, while indomethacin had no effect on ERPF and augmented remnant kidney weight. It appears effects of captopril and indomethacin on intrarenal hemodynamics in the residual kidney were counteractive, and that conjoint therapy in renal disease should be approached with caution.
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PMID:Captopril or prostaglandin E1 ameliorate adverse renal hemodynamic effects of indomethacin in uninephrectomized rats. 264 48

Mean arterial blood pressure was measured over a 24-hour period from the femoral artery of conscious, unrestrained spontaneously hypertensive rats. Oral administration of the angiotensin converting enzyme inhibitor CGS 16617 significantly lowered mean arterial pressure. In contrast, both the thromboxane synthase inhibitor CGS 12970 and the thromboxane receptor antagonist BM 13505 lacked an antihypertensive action in the spontaneously hypertensive rat. When administered concurrently, the thromboxane synthase inhibitor CGS 12970 potentiated the antihypertensive action of the angiotensin converting enzyme inhibitor CGS 16617. This effect was not observed with the thromboxane receptor antagonist BM 13505. In addition to CGS 16617, CGS 12970 also potentiated the hypotensive effect of two structurally dissimilar angiotensin converting enzyme inhibitors, benazapril HCL and captopril. Indomethacin blocked the thromboxane synthase inhibition-induced potentiation of the antihypertensive action of angiotensin converting enzyme inhibitors. The thromboxane synthase inhibitor CGS 12970 had no effect on the hypotension induced by hydralazine, indicating that the hypotension is not a nonspecific action related to the fall in blood pressure. These results may suggest that converting enzyme inhibition augments the levels and actions of a hormone that stimulates prostaglandin formation. It is well established that thromboxane synthase inhibitors eliminate the formation of the vasoconstrictor thromboxane A2 and allow reorientation of eicosanoid production toward the formation of vasodilating prostaglandins, which could enhance the antihypertensive action of angiotensin converting enzyme inhibitors.
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PMID:Thromboxane synthase inhibition enhances action of converting enzyme inhibitors. 291 Aug 14


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