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 effects of converting enzyme inhibition on coronary and systemic hemodynamics in the presence of a chronically activated renin-angiotensin system were investigated in five renovascular hypertensive patients with no ECG/echocardiographic evidence of left ventricular hypertrophy. Coronary blood flow (CBF, thermodilution technique), intra-arterial blood pressure, AVO2 difference (coronary sinus), heart rate, and coronary vascular resistance were measured at rest, during isometric exercise (handgrip to 50% of maximal effort for 3 min) before and 60 min after 2.5 mg of oral cilazapril. The drug induced a prompt, significant decrease in mean arterial pressure and a sustained increase in CBF. The performance of handgrip after cilazapril resulted in higher increases in CBF for a given increase in myocardial oxygen requirements. These observations suggest that angiotensin II (Ang II) maintains the ability to alter the control mechanisms of CBF even under long-term conditions and that converting enzyme inhibition reverses the Ang II-induced effects on coronary hemodynamics.
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PMID:Acute effects of cilazapril on coronary hemodynamics in patients with renovascular hypertension. 138 89

The effect of the angiotensin converting enzyme (ACE) inhibitor fosinopril sodium on regional cerebral blood flow (rCBF) was investigated in 8 patients with moderate essential hypertension. A constant dose of chlorthalidone (25 mg/day) was given to stimulate the renin angiotensin system, and fosinopril sodium was given in incremental doses (10 to 40 mg/day) with the aim of obtaining a diastolic blood pressure at or below 90 mm Hg. Regional CBF was measured with xenon-133 inhalation tomography. Repetitive measurements were made at the start of treatment and again after 4 to 12 weeks treatment in the resting supine position, and during lower body negative pressure (LBNP) as a substitute for the upright position. Four hours after the first 10 mg dose of fosinopril the mean arterial pressure (MAP) had been reduced from 127 +/- 13 mm Hg to 105 +/- 9 mm Hg (P less than .01) without any significant change in mean CBF (55 +/- 9 mL/(100 g X min) at baseline versus 52 +/- 9 mL/(100 g X min) after fosinopril). After prolonged treatment with chlorthalidone and fosinopril, mean CBF was still unchanged from baseline levels, when measured 4 and 24 h after a single dose of fosinopril, despite a 10% reduction in MAP (P less than .01). LBNP did not lead to any significant change in rCBF. The regional distribution of CBF was normal in all patients throughout the study. We conclude that treatment with fosinopril sodium causes a moderate fall in blood pressure without any adverse effects on rCBF.
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PMID:The effect of fosinopril sodium on cerebral blood flow in moderate essential hypertension. 214 29

The present single-blind, randomised, cross-over, placebo-controlled study was set up to compare the first-dose effects upon blood pressure (BP) and cerebral blood flow (CBF, measured by Xenon inhalation) of a single oral dose of atenolol 50 mg and enalapril 5 mg in ten hypertensive patients receiving a thiazide diuretic. It was found that a) the timing and degree of fall in BP after the first dose of atenolol and enalapril on a diuretic background were similar and generally not associated with symptoms or a fall in CBF, and b) dizziness, which is sometimes associated with the first-dose effect of ACE inhibitors in hypertensives on diuretics, can occasionally occur accompanied by a substantial fall (43%) in CBF in the absence of marked falls in systolic blood pressure. It is suggested that the latter event may be linked to a disturbance of cerebral autoregulation in part dependent on localised renin-angiotensin systems.
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PMID:First-dose effects of enalapril and atenolol upon blood pressure and cerebral blood flow in patients with mild hypertension on diuretic therapy. 219 32

There is evidence of an intrinsic renin-angiotensin system in the brain. The goal of the study was to determine whether stimulation of endogenous angiotensin production by applying renin to the brain surface has an effect on pial arteriolar caliber and CBF. Pial vessel diameters were measured through a closed cranial window in anesthetized rabbits. Percent changes of blood flow in the cortical area under the cranial window were simultaneously measured by laser-Doppler flowmetry. Topical application of 0.01-0.1 U/ml renin induced maximum dilation of 18.9 +/- 4% (mean +/- SD) of pial arterioles within 2 min. Arteriolar calibers thereafter decreased slowly. Flow gradually increased to peak at 38 +/- 15% 50 min after renin application. Angiotensin I levels in jugular blood, as measured by radioimmunoassay, increased to a peak 40 min after topical renin application. Angiotensin II levels in jugular blood and both angiotensin I and II levels in blood samples from the femoral artery did not change. Diameter and flow changes were inhibited by intravenous pretreatment with the converting enzyme blocker captopril (10 mg/kg body wt i.v.). Captopril did not affect the vasodilation and flow increase in response to hypercapnia. Topically applied captopril (10(-5) M) blocked renin-induced arteriolar dilation. We conclude that renin increases pial arteriolar diameters and cortical blood flow in the rabbit brain. Stimulation of angiotensin production is likely to be a mediator of this response.
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PMID:Effect of renin on brain arterioles and cerebral blood flow in rabbits. 896 12

Adult Ren-2 gene transgenic rats, TGR(mRen-2)27, exhibit elevated circulating and kidney angiotensin II (Ang II) levels in the presence of severe hypertension. The aim of this study was to examine whether AT1 and AT2 receptors in the kidney and renal hemodynamic and tubular responses to blockade of these receptors were altered in the Ren-2 gene transgenic rats during the maintenance phase of hypertension. Renal AT1 and AT2 receptors were mapped by in vitro autoradiography (n=8), and the effects of blockade of these receptors on mean arterial pressure (MAP), heart rate (HR), and renal cortical (CBF) and medullary blood flows (MBF) were studied in anaesthetized, adult age-matched male homozygous TGR rats (n=12) and Sprague-Dawley (SD) rats (n=7). TGR rats showed higher basal MAP (P<0.001), heart and kidney weight (P<0.001), plasma renin activity (P<0.05) and plasma Ang II level (P<0.05), and CBF (P<0.05) and MBF (P<0.05) than SD rats. AT1 receptor binding was significantly increased in the glomeruli, proximal tubules, and the inner stripe of the outer medulla of TGR rats (P<0.01), while the AT2 receptor binding was low at all renal sites of TGR and SD rats. Immunohistochemistry revealed that this increased AT1 receptor labeling occurred mainly in vascular smooth muscle layer of intrarenal blood vessels including afferent and efferent arterioles, juxtaglomerular apparatus, glomerular mesangial cells, proximal tubular cells, and renomedullary interstitial cells (RMICs) in the transgenic rats. Blockade of AT1 receptors with losartan in TGR rats markedly reduced MAP to the normotensive level (P<0.001) without altering HR. Both CBF (P<0.005) and MBF (P<0.05) were significantly increased by losartan in the transgenic rats. By contrast, losartan only caused a smaller decrease in MAP and an increase in renal CBF in SD rats (P<0.05). PD 123319 was without any renal effect in both SD and TGR rats. These findings suggest that markedly increased AT1 receptors in renal vasculature, glomerular mesangial cells, and RMICs in the presence of fulminant hypertension and elevated circulating and tissue Ang II levels may play an important role in the maintenance of hypertension in the Ren-2 gene transgenic rats.
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PMID:Roles of AT1 and AT2 receptors in the hypertensive Ren-2 gene transgenic rat kidney. 993 Nov 28

To determine how endothelins affect regional kidney blood flow and responses to increased renal artery pressure (RAP), an extracorporeal circuit was established to control RAP independent of the mean systemic arterial pressure (MAP). RAP was first set at approximately 65 mm Hg, and endothelin-1 (1 ng/kg/min for 30 min then 0.4 ng/kg/min) or vehicle was infused into the renal artery, or the ET(A)/ET(B) antagonist TAK-044 (3 mg/kg plus 3 mg/kg/h) or vehicle was administered intravenously. RAP was then progressively increased in steps from approximately 65 to approximately 160 mm Hg. When RAP was approximately 65 mm Hg, endothelin-1 increased renal vascular resistance (RVR, 72%), and reduced cortical (CBF, 26%) but not medullary blood flow (MBF). TAK-044 reduced MAP (12%) and RVR (15%) and increased CBF (21%) but not MBF. When RAP was increased, renal blood flow (RBF), glomerular filtration rate, and urine and sodium excretion increased, while MAP fell. These responses were unaffected by endothelin-1. TAK-044 potentiated the increases in RBF and reductions in MAP in response to increased RAP, but did not affect urine and sodium excretion. Plasma renin activity was reduced by endothelin-1 and increased by TAK-044. Thus, both exogenous and endogenous endothelins reduce CBF but not MBF, and reduce plasma renin activity, but neither affect pressure natriuresis.
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PMID:Effects of renal arterial endothelin-1 and endogenous endothelins on regional kidney blood flow and renal antihypertensive mechanisms in anesthetized rabbits. 1107 Apr 16

Renin gene expression is subject to complex developmental and tissue-specific regulation. A comparison of the promoter sequences of the human, rat, and mouse renin genes has revealed a highly conserved sequence homologous to the DNA recognition sequence for CBF1 (CSL/RBP-Jkappa/Su(H)/LAG1/RBPSUH). Electrophoretic mobility shift assays document that As4.1 cell nuclear protein complex binding to the putative rat renin CBF1-binding site (-175 to -168 bp) contains CBF1. Transient transfection analyses in COS-7 cells further document that a CBF1-VP16 fusion protein and the intracellular domain of Notch1 robustly activate a promoter containing multiple copies of the rat renin CBF1-binding site. An Ets-binding site (-143 to -138 bp) has also been identified in the rat renin promoter by sequence comparisons and electrophoretic mobility shift assays. Transcription factor Ets-1 is capable of activating the rat renin promoter through the Ets-binding site. Mutation of the CBF-binding site significantly increases transcriptional activity of the rat renin promoter in Calu-6 and COS-7 cells but not in As4.1 cells, whereas mutation of the Ets-binding site reduces promoter activity of the rat renin gene in all three cell lines. Finally, we show that the intracellular domain of Notch1, Ets-1, and HOXD10.PBX1b.PREP1 activate the rat renin promoter cooperatively in COS-7 cells. These results strongly suggest that the renin gene is a downstream target of the Notch signaling pathway.
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PMID:Activation of the rat renin promoter by HOXD10.PBX1b.PREP1, Ets-1, and the intracellular domain of notch. 1579 57

We investigated the roles of the renin-angiotensin system and the significance of interactions between angiotensin II and nitric oxide, in responses of regional kidney perfusion to electrical renal nerve stimulation (RNS) in pentobarbital sodium-anesthetized rabbits. Under control conditions, RNS (0.5-8 Hz) reduced total renal blood flow (RBF; -89 +/- 3% at 8 Hz) and cortical perfusion (CBF; -90 +/- 2% at 8 Hz) more than medullary perfusion (MBF; -55 +/- 5% at 8 Hz). Angiotensin II type 1 (AT(1))-receptor antagonism (candesartan) blunted RNS-induced reductions in RBF (P = 0.03), CBF (P = 0.007), and MBF (P = 0.04), particularly at 4 and 8 Hz. Nitric oxide synthase inhibition with N(G)-nitro-L-arginine (L-NNA) enhanced RBF (P = 0.003), CBF (P = 0.001), and MBF (P = 0.03) responses to RNS, particularly at frequencies of 2 Hz and less. After candesartan pretreatment, L-NNA significantly enhanced RNS-induced reductions in RBF (P = 0.04) and CBF (P = 0.007) but not MBF (P = 0.66). Renal arterial infusion of angiotensin II (5 ng.kg(-1).min(-1)) selectively enhanced responses of MBF to RNS in L-NNA-pretreated but not in vehicle-pretreated rabbits. In contrast, greater doses of angiotensin II (5-15 ng.kg(-1).min(-1)) blunted responses of MBF to RNS in rabbits with intact nitric oxide synthase. These results suggest that endogenous angiotensin II enhances, whereas nitric oxide blunts, neurally mediated vasoconstriction in the renal cortical and medullary circulations. In the renal medulla, but not the cortex, angiotensin II also appears to be able to blunt neurally mediated vasoconstriction.
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PMID:Angiotensin II and nitric oxide in neural control of intrarenal blood flow. 1589 Jul 88