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 steroidogenic and pressor activities of the nonapeptide (des-Asp1) angiotensin I [(des-Asp)-AI] were tested in conscious rats. (des-Asp)-AI caused dose related increases in mean arterial pressure (MAP), serum aldosterone, and serum corticosterone in doses between 3 and 3,000 ng/kg/min. (des-Asp)-AI was 14% as potent as angiotensin I and angiotensin II and 60% as potent as (des-Asp1) angiotensin II [des-Asp)-AII] in raising MAP. (des-Asp)-AI was less active than AI, AII, or (des-Asp)-AII in causing increased release of aldosterone, possessing only 8%, 11%, and 17% of the potency of AII, (des-Asp)-AII, and AI, respectively. Each of these angiotensin peptides was equally potent in elevating serum corticosterone levels. Infusions of a nonapeptide inhibitor of converting enzyme (CEI, 0.5 mg/kg/min iv) did not alter control MAP or blood pressure responses to AII or (des-Asp-)-AII but inhibited equally the blood pressure effects of AI and (des-Asp)-AI. CEI also inhibited the ability of (des-Asp)-AI (67% inhibition) and AI (34% inhibition) to increase the serum aldosterone concentration, but had no effect on basal aldosterone levels. These data indicate that (des-Asp)-AI has pressor and steroidogenic effects, but requires conversion to (des-Asp)-AII for a major portion of its activity. These results further substantiate the hypothesis that (des-Asp)-AII, recently recognized as a hormone of the renin-angiotensin system, may be produced without the formation of AII as an intermediate and provide in vivo evidence for the conversion of (des-Asp)-AI to (des-Asp)-AII.
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PMID:(Des-Asp1) angiotensin I: a study of its pressor and steroidogenic activities in conscious rats. 18 7

Kininase II (angiotensin I-converting enzyme) is generally accepted to be the enzyme responsible for the conversion of angiotensin I (A I) to angiotensin II (A II). This study examined the response of the microvasculature of the hamster cheek pouch to the local application of A I, A II, and the renin substrate, tetradecapeptide (TDP). A I and TDP caused a localized vasoconstriction that was not blocked by converting enzyme inhibitors (CEI: BPF5a for A I and BPF5a and the nonapeptide inhibitor for TDP). However, both the A II antagonist [Sar1, Ala8]angiotensin II and the antiserum to A II blocked completely the A I- and TDP-induced vasoconstriction. Sixty-eight percent of the applied A I was converted to A II in the presence of CEI as well as in its absence. It is concluded that the vasculature of the hamster cheek pouch converts significant amounts of A I to A II by a route that does not involve kininase II.
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PMID:Direct evidence for the presence of a different converting enzyme in the hamster cheek pouch. 21 48

In humans, blockade of the renin-angiotensin system with angiotensin converting-enzyme inhibitors (ANG CEI) prevents the rise in blood pressure associated with the administration of recombinant human erythropoietin (rhEPO). This study was conducted to determine whether rhEPO elevates blood pressure in normal Wistar rats and whether the renin-ANG system is affected. Groups of 10 rats each were given rhEPO, ANG CEI (enalapril), rhEPO + ANG CEI, or vehicle. Renin and/or renin substrate mRNA was measured in aortas, kidney, and heart; renin activity (PRA), inactive renin, and renin substrate were measured in plasma. rhEPO raised blood pressure in the normal rat without changing the plasma renin system. ANG CEI prevented this blood pressure rise. Renin-specific mRNA was increased by rhEPO in renal tissue, and renin substrate mRNA was significantly elevated in the kidney and aorta. mRNA for renin and renin substrate were not altered in the heart. In both aorta and kidney, a significant correlation was observed between renin substrate mRNA and blood pressure. The data indicate that rhEPO modulates specific tissue renin-ANG systems, which may contribute to blood pressure elevation.
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PMID:Influence of recombinant human erythropoietin on blood pressure and tissue renin-angiotensin systems. 195 90

The role of the brain renin-angiotensin system (RAS) in the baroreflex regulation of renal sympathetic nerve activity (RSNA) and heart rate (HR) was studied in conscious rabbits. RSNA and HR were recorded during slow ramp changes in mean arterial pressure (MAP) before and after intraventricular infusion of 1) angiotensin II (ANG II), 2) ANG II receptor antagonist, [Sar1,Ile8]ANG II, or 3) converting enzyme inhibitor (CEI, enalaprilat). Central ANG II increased resting MAP and RSNA by 10.6 +/- 0.9 mmHg and 21 +/- 7%, respectively, but did not alter HR. There was a marked increase of 107 +/- 15% in the maximum RSNA evoked by slowly lowering MAP. In contrast, maximum reflex tachycardia was only modestly elevated, and baroreflex inhibition of RSNA and HR during MAP rises was unaffected. Central [Sar1,Ile8]ANG II had no effect on RSNA or HR, either at rest or during baroreflex responses, while CEI slightly enhanced maximal reflex responses. Thus exogenous ANG II causes a powerful excitation of renal sympathetic motoneurons, the magnitude of which is revealed when tonic baroreceptor inhibition is removed during transient pressure falls. However, in quietly resting conscious rabbits, we found no evidence for a tonic influence of endogenous ANG II on these neurons, and the physiological stimuli required for their activation by the brain RAS remain to be found.
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PMID:Influence of brain renin-angiotensin system on renal sympathetic and cardiac baroreflexes in conscious rabbits. 200 Sep 72

Recent observations implicate angiotensin-II (AII) as a possible PRL-releasing factor. These observations prompted us to investigate the role of the renin-angiotensin system in PRL release in man. Nine normal volunteers ingesting a 20-40 mmol/day sodium, 70 mmol/day potassium diet and eight normal volunteers ingesting a 120 mmol/day sodium, 70 mmol/day potassium diet were infused with metoclopramide (2.5 mg over 1 min) and later with TRH (500 micrograms), two agents known to cause PRL release. The infusions were repeated after 36 h of oral administration of converting enzyme inhibitor [CEI; captopril (50 mg, orally, four times daily) or enalapril (5 mg, orally, twice daily)]. On a separate occasion, AII was infused at 10 ng/kg.h for 1 h into normal volunteers on normal salt diet. CEI administration lowered mean arterial pressure by 6-7 mm Hg and stimulated the release of active renin. The PRL responses on low and normal salt diet as well as before and after CEI were not statistically different. There was also no difference in the PRL responses of patients placed on captopril vs. those on enalapril. AII increased blood pressure by 11-25 mm Hg, but did not increase PRL significantly above basal concentrations during the control dextrose infusion. Five hyperprolactinemic volunteers were also given CEI for up to 4 weeks. They demonstrated no significant change in serum PRL levels. We conclude that AII in the pituitary does not significantly alter either basal PRL levels or metoclopramide- and TRH-induced PRL responses in normal subjects on low and high salt diets. In addition, CEI is not a useful therapy in patients with pathological hyperprolactinemia. These findings, however, do not exclude a role for AII in physiological regulation, since CEI does not cross the blood-brain barrier and would not be expected to alter hypothalamic AII.
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PMID:The effect of angiotensin-converting enzyme inhibition on prolactin responses in normal and hyperprolactinemic subjects. 250 32

To assess the renin-angiotensin (RA) dependence of evolving neonatally induced coarctation hypertension (NICH) in inbred pups, we randomized sex-matched littermates to a high dose of converting-enzyme inhibitor (CEI:MK-421) or placebo from the time of neonatal aortic banding (coarcted) vs. no banding (control). In phase 1 studies, pups were examined serially on normal diet (Bagby and Fuchs, Hypertension In press.): chronic CEI lowered systolic blood pressure (BP) equally in coarcted and controls and failed to prevent systolic BP excess in coarcted dogs. In phase 2 studies, the same pups were exposed to a low sodium (LS) diet at 4 mo of age, a time when the untreated NICH model exhibits increased forelimb systolic BP. Measurements of systolic BP, RA components, renal function, and extracellular volume (ECV) were made before and serially during 12 days on the LS diet. Responses of coarcted and control pups to the LS diet were similar, with or without CEI, providing no evidence for exaggerated angiotensin II (ANG II) dependence in evolving NICH. Independently of coarctation status, chronic CEI significantly modified RA and renal functional responses to the LS diet: a greater renin rise but abnormal renin substrate fall, thus no rise in ANG I or ANG I generation rate; a greater rise in creatinine and a trend toward a greater fall in glomerular filtration rate (GFR). Despite these findings compatible with sustained ANG II deficit, chronic CEI unexpectedly failed to impair maintenance of systolic BP during a superimposed LS diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic CEI alters effect of low Na+ diet in normal and coarcted pups. I. BP, renin, and GFR. 253 42

To assess angiotensin (ANG II) dependence of evolving neonatally induced coarctation hypertension (NICH) in inbred pups, we randomized sex-matched littermates to high-dose converting enzyme inhibitor (CEI: MK-421, 3 mg/kg) or placebo from the time of neonatal aortic banding (coarcted) vs. no banding (control). During phase 1 studies over 4 mo postbanding during ad libitum Na+ intake (Bagby and Fuchs, Hypertension Dallas in press). CEI failed to prevent evolution of proximal blood pressure (BP) excess or to impair renal function. Phase 2 studies examine, in the same pups, responses to low Na+ (LS) diet superimposed on chronic CEI at 4 mo, timed to allow development of BP increase in untreated NICH. The present report details metabolic handling and balances of Na+, K+, and fluid for 3 days before (normal Na+ intake) and daily for 11 days after initiation of LS diet, a companion paper describes BP, renin-angiotensin (RA), and renal functional responses. In no case did metabolic responses of coarcted pups to LS diet differ from those of controls, whether on CEI or placebo, whereas responses to LS diet and to CEI reveal positive findings of independent interest. LS diet induced expected renal and fecal Na+ conservation, no net effect on K+ balance, and, despite unexpected free-water diuresis, mild hyponatremia. Chronic CEI impaired maximal renal (but not fecal) Na+ conservation during LS diet, caused exaggerated free-water diuresis but no change in fluid balance, and thus, with the larger Na+ deficit, accounted for greater hyponatremia. CEI caused no net effect on K+ balance. Results indicate normal renal handling of fluid, Na+, and K+ in evolving NICH and provide no evidence for selective intrarenal RA activation or exaggerated ANG II dependence. Findings also suggest that, during LS diet, ANG II is 1) essential for maximum renal Na+ conservation and normal free-water handling, and 2) not essential for fecal Na+ and water conservation or for maintenance of normal water and K+ balances. Results are also compatible with a CEI-induced thirst stimulation and/or osmotic insensitivity and with functional vasopressin deficiency during LS diet.
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PMID:Chronic CEI alters effect of low Na+ diet in normal and coarcted pups. II. Na+ and H2O balance. 253 43

To define the role of vasopressin as a vasoconstrictor hormone in sodium depletion, systemic hemodynamics and regional blood flow distribution were examined in conscious Sprague-Dawley rats after 6 days of a low-sodium diet. Studies were performed after selective or combined blockade with the vasopressin antagonist [d(CH2)5Tyr(Me)]AVP (AVPA), enalaprilat (CEI), and phentolamine (PHENTOL). Plasma levels of vasopressin were increased significantly after CEI and increased further after PHENTOL and CEI plus PHENTOL. AVPA had no effect on blood pressure, whether given alone or in the presence of PHENTOL, CEI, or CEI plus PHENTOL. Significant falls in peripheral vascular resistance associated with reflex increases in cardiac output were observed when AVPA was given to animals pretreated with either CEI or PHENTOL but not both. AVPA alone produced no significant changes in regional blood flow distribution, but a vasoconstrictor action of vasopressin in the renal vascular bed was revealed after prior treatment with CEI or PHENTOL. Muscle blood flow was also increased in the PHENTOL plus AVPA group compared with the PHENTOL group. No significant additional effects of AVPA were revealed by pretreatment with CEI, PHENTOL, or CEI plus PHENTOL for mesenteric, hepatic, splenic, or cerebral vascular beds. It is suggested that vasopressin acts as a vasoconstrictor hormone in conscious sodium-depleted rats when either the renin-angiotensin system or alpha-adrenergic system is inhibited but not when both systems are blocked. The renal vascular bed is an important site for vasopressin-induced vasoconstriction under these circumstances.
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PMID:Vasoconstrictor role for vasopressin in conscious, sodium-depleted rats. 288 70

1. The role of vasopressin in cardiovascular adaptation to sodium depletion was examined in rats after 6 days on a low sodium diet. Studies were performed after selective or combined blockade with d(CH2)5 Tyr(Me)AVP (AVPA), enalaprilat (CEI) and phentolamine (PHENTOL). AVPA alone had no effect on systemic haemodynamics or regional blood flow distribution. After CEI or PHENTOL pretreatment, AVPA led to significant falls in peripheral resistance and increases in cardiac output and renal blood flow. In sodium depletion, endogenous vasopressin acts as a vasoconstrictor hormone, particularly in the kidney, when either the renin-angiotensin or alpha-adrenergic system is inhibited.
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PMID:Interaction of vasopressin, angiotensin and alpha-adrenergic system in sodium depletion in the rat. 288 51

To evaluate the effects of angiotensin converting enzyme inhibition (SQ 20881, CEI) on superficial nephron function of the non-clipped kidney in Goldblatt hypertensive rats in the absence of alterations in renal arterial pressure, control renal arterial pressure (RAP) was reduced first to the range generally obtained during CEI (124 +/- 4 mm Hg). RAP was maintained during the CEI period by adjustment of a suprarenal aortic clamp. At the reduced RAP, whole kidney and single nephron glomerular filtration rates (GFR) were reduced from the hypertensive levels and were lower than the measurements in normotensive control rats. During CEI, whole kidney GFR and single nephron GFR increased by 55 and 42%, respectively. There were decreases in absolute as well as fractional proximal reabsorption rates. In the intermediate nephron segment, fractional reabsorption was decreased, but absolute fluid reabsorption increased in proportion to the increased delivery rate. Proximal tubule and peritubular capillary hydrostatic pressures increased significantly during CEI also. These results indicate that an increased activity of the renin-angiotensin system occurring in Goldblatt hypertensive rats subjected to aortic constriction exerts effects to lower GFR and increase proximal reabsorption rate. The concomitant superficial nephron and whole kidney GFR responses to CEI when arterial pressure was maintained suggests that the pre-existing levels of angiotensin exerted similar influences on the total nephron population.
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PMID:Nephron responses to converting enzyme inhibition in non-clipped kidney of Goldblatt hypertensive rat at normotensive pressures. 300 54


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