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)

Inhibitors of nitric oxide (NO) synthesis increase blood pressure and decrease regional blood flow. We investigated whether blockade of the renin-angiotensin, sympathetic nervous, prostaglandin or vasopressin systems attenuates the effects of the NO synthesis inhibitor NG-nitro-L-arginine (L-NOARG) on mean arterial pressure and renal blood flow in anesthetized male Sprague-Dawley rats. Treatment with L-NOARG (10 mg kg-1, i.v. bolus plus infusion at 20 mg kg-1 hr-1) increased mean arterial pressure from 113 +/- 2 to 133 +/- 4 mm Hg, decreased renal blood flow from 7.7 +/- 0.6 to 4.3 +/- 0.6 ml min-1 g-1 and increased renal vascular resistance from 15.8 +/- 1.8 to 36.9 +/- 6.1 mm Hg/ml min-1 g-1. These effects were attenuated in rats pretreated with L-arginine to interfere with the inhibitory action of L-NOARG on NO synthesis, but not in rats pretreated with D-arginine. Acetylcholine did not relax aortic rings taken from rats treated with L-NOARG, consistent with inhibition of NO-mediated vasorelaxation. The pressor and renal vasoconstrictor effects of L-NOARG were not impaired in rats separately pretreated with either chlorisondamine, captopril, prazosin, indomethacin or d(CH2)5Tyr(Me)AVP, or in rats pretreated with chlorisondamine, captopril and indomethacin in combination. Collectively, these data argue against significant contribution of the sympathetic nervous system, the renin-angiotensin system, vasopressor prostanoids or vasopressin to the mechanisms of L-NOARG-induced elevation of mean arterial pressure and renal vasoconstriction in anesthetized rats.
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PMID:Pressor and renal vasoconstrictor effects of NG-nitro-L-arginine as affected by blockade of pressor mechanisms mediated by the sympathetic nervous system, angiotensin, prostanoids and vasopressin. 156 Mar 71

1. The effect of an intracisternal injection of 20 micrograms kg-1 of acetylcholine was studied on systolic and diastolic blood pressures, heart rate, and plasma levels of noradrenaline, adrenaline, vasopressin, plasma renin activity and atrial natriuretic factor in chloralose-anaesthetized dogs, 8 of which were normal and 7 with diabetes insipidus (deprived of vasopressin secretion by surgical lesion of the hypothalamoneurohypophysial system). 2. Acetylcholine significantly increased systolic and diastolic blood pressures in both groups of animals. However, the rise in blood pressure was significantly shorter lived in the dogs with diabetes insipidus. 3. Acetylcholine significantly increased plasma levels of noradrenaline but not adrenaline in control animals and in dogs with diabetes insipidus. Noradrenaline and adrenaline responses after acetylcholine were not different in the two groups of animals. 4. Acetylcholine induced a significant increase in vasopressin plasma levels only in control animals while in dogs with diabetes insipidus vasopressin remained at nearly undetectable levels. 5. Acetylcholine significantly increased atrial natriuretic factor plasma levels only in control dogs. 6. Although plasma renin activity increased in both groups of animals after the i.c. injection of acetylcholine, this change was not significant in any group. 7. These results suggest that, in the anaesthetized dog, the central injection of acetylcholine induces a rise in blood pressure through both an increase in sympathetic outflow and a release of vasopressin.
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PMID:Cardiovascular effects of central injection of acetylcholine in anaesthetized dogs: a role for vasopressin release. 214 57

Studies were run to determine whether the renal microvascular endothelium influences renin release. Blood-free rat renal cortical slices were incubated in a bicarbonate buffer for 60 min and sampled at 30 and 60 min to determine renin concentration and at 60 min for prostaglandin (PG) E2 and I2 (6-keto-PGF1 alpha) synthesis. Stimulation by 10(-6) M melittin of endogenous PGs simultaneously increased renin release, PGE2, and PGI2 synthesis, and all were inhibited by 1.6 x 10(-6) M meclofenamate. Renin release was stimulated with isoproterenol [26.2 +/- 2.4 ng angiotensin I (ANG I) .h-1.mg-1.30 min-1; P less than 0.001], PGI2 (32.3 +/- 7.4 ng ANG I.h-1.mg-1.mg-1.30 min-1; P less than 0.005), and PGE2 (25.7 +/- 2.8 ng ANG I.h-1.mg-1.30 min-1, P less than 0.001). Acetylcholine did not affect basal renin but potentiated the response to PGE2 by 80% (46.0 +/- 5.8 ng ANG I.h-1.mg-1.30 min-1; P less than 0.001). Atropine (10(-7) M) reversed this potentiation. Deendothelialization of renal microvessels with H2O2 eliminated PGI2, but neither PGE2 nor renin release, and reversed acetylcholine-potentiation of PGE2-stimulated renin release as did meclofenamate. Hemoglobin increased PGE2-stimulated renin similarly to acetylcholine. These studies suggest that stimulating the endothelium with acetylcholine results in selective potentiation of PGE2-stimulated renin release, which may be mediated through some cyclooxygenase product and is independent of endothelium-derived relaxing factor. Thus the renal endothelium may influence or modulate renin release.
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PMID:Possible endothelial modulation of prostaglandin-stimulated renin release. 218 36

The effect of vanadate (0.5 mumol/min) on renin secretory rate (RSR) of the kidney has been studied in nembutal-anesthetized, volume-expanded dogs. Intrarenal vanadate infusion caused a 69.3 +/- 8.8% decrease in RSR. This was accompanied by marked decreases in renal blood flow (RBF), glomerular filtration rate (GFR) and fractional excretion of sodium (FENa). Renal vascular resistance rose from 1.3 +/- 0.09 to 6.1 +/- 2.3 mm Hg/ml/min (P less than .0005). Papaverine infusion partially blunted the effect of vanadate on RSR (RSR only fell to 42. +/- 10% of basal values). The decreases in RBF and GFR were also less and FENa slightly higher than normal. Acetylcholine prevented the effects of vanadate more fully. There was no fall in RBF, GFR or FENa and it basically abolished the fall in RSR which fell only 19.4 +/- 25.3 of control (P = N.S.). Nifedipine (a slow Ca++ channels blocker) also prevented the fall in RBF, GFR and FENa induced by vanadate. RSR did not change significantly (7.8 +/- 10.9%). These results clearly demonstrate that vanadate is a potent inhibitor of renin secretion and suggest that inhibition of smooth muscle Na+, K+, adenasine triphosphatase and changes in the cystosolic concentration of Na and Ca are involved in its mechanism. Changes in perfusion pressure and sodium delivery to the macula densa appear to have little if any role in the inhibition.
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PMID:Effect of sodium orthovanadate on renal renin secretion in vivo. 628 12

1. The effects of the state of renal vascular tone during induction of renal artery stenosis on the subsequent systemic blood pressure and renin responses have been studied in chronically instrumented, conscious dogs. 2. In one group of dogs, renal vascular tone was altered by brief (2-3 min) renal artery infusions of ACh, saline, methoxamine or angiotensin II during narrowing of the renal artery to reduce distal pressure to 40 mmHg. The infusions were turned off 1 min later. 3. The more vasoconstricted the kidney at the time of stenosis, the slower was the restoration of distal renal artery pressure and the greater the rises in systemic blood pressure, plasma renin activity (PRA) and effective stenosis resistance. At the end of 1 hr of stenosis, the rises in systemic blood pressure were 4.3 +/- 3.3, 11.3 +/- 3.3, 28.9 +/- 3.3 and 26.3 +/- 2.8 mmHg for the ACh, saline, methoxamine and angiotensin II-infused dogs respectively; rises in PRA were 0.3 +/- 0.24, 1.18 +/- 0.42, 5.09 +/- 1.38 and 4.02 +/- 0.74 ng/ml. per hr respectively. 4. In another group of dogs a given aortic-renal artery pressure gradient was produced on two occasions: (i) with the animal conscious; (ii) under brief sodium pentobarbitone anaesthesia and preparation for surgery. After 24 hr systemic blood pressure had risen by 15.7 +/- 3.6 mmHg above initial values when stenosis was induced under anaesthesia (P < 0.05) and only by 1.2 +/- 3.6 mmHg (N.S.) when it was induced with the animal conscious. Corresponding rises in PRA were 1.29 +/- 0.42 (P < 0.05) and 0.25 +/- 0.11 (N.S.) ng/ml. per hr. Establishment of a given gradient in the high vascular resistance kidney of the anaesthetized dog thus requires greater narrowing of the renal artery than in the lower resistance renal bed of the conscious animal. 5. The tone of the renal vascular bed is a major determinant of the severity of renal artery stenosis.
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PMID:The importance of renal vascular tone in determining the severity of renal artery stenosis in dogs. 744 56

We investigated the interaction between nitric oxide and the renin angiotensin system in regulating isolated aortic tension and mean arterial pressure in renal hypertensive rats (RHR). Acetylcholine (ACh) relaxed aorta precontracted with norepinephrine from RHR significantly less than that from normotensive rats (NR) (Emax: 34.3% and 86.0%, respectively, P < 0.01). The ACh-induced relaxation was significantly enhanced by losartan (P < 0.05) and completely abolished by removal of endothelium or NG-nitro-L-arginine methyl ester (L-NAME). ACh lowered the mean arterial pressure slightly less effectively in RHR than in NR (6.8 and 13.0 mmHg, respectively, at 0.1 microgram/kg), whereas the depressor effect was reduced by L-NAME (-15.5 and 10.3 mmHg, respectively, at 0.1 microgram/kg), but rather enhanced by further treatment with losartan (9.9 (P < 0.05) and 17.3 mmHg, respectively, at 0.1 microgram/kg). Angiotensin II induced similar contractile and pressor responses in both RHR and NR, and these effects were significantly enhanced by L-NAME, except for the pressor effect in RHR. L-NAME induced a similar pressor response in RHR and NR (15.9 and 15.2 mmHg, respectively, at 0.1 mg/kg), the effect being decreased by pretreatment with losartan. Losartan induced a depressor response that was smaller in RHR than in NR (34.0 and 48.8 mmHg, respectively, at 0.3 mg/kg), and the response was significantly reduced by L-NAME. These results suggest that nitric oxide interacts with the renin angiotensin system to control the vascular tension and systemic arterial circulation in RHR.
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PMID:Interaction of nitric oxide and the renin angiotensin system in renal hypertensive rats. 919 1

Atherogenic lipoproteins accumulate in the arterial wall as well as within the glomerulus and may accelerate vascular and glomerular injury. We therefore assessed whether oxidized low density lipoprotein (LDL) and lipoprotein(a) [Lp(a)] influence three major systems: (i) endothelium-dependent vasodilation, (ii) renin release of juxtaglomerular (JG) cells, and (iii) proliferation and viability of mesangial cells (MC). Lipoproteins were prepared from human plasma. Renal arteries were obtained from rabbits and JG as well as MC cells from mouse, rat and human kidneys. Dilator responses were detected in isolated arterial segments by a photoelectric device. Renin activity of JG cells was measured in culture supernatants and cells and DNA synthesis by 3H-thymidine incorporation in MC. Acetylcholine-induced, endothelium-dependent dilator responses of renal arteries were not significantly attenuated after incubation with native Lp(a). However, exposure to in vitro oxidized Lp(a) suppressed dilator responses in a dose-dependent manner. Using a chemiluminescence assay, we could detect increased O2- production by arteries pretreated with oxidized Lp(a), which suggested that enhanced nitric oxide (NO) inactivation by O2- might be the underlying mechanism of impairment of endothelium-dependent dilations. In general, oxidized Lp(a) was far more potent than oxidized LDL in this effect. In JG cells, both oxidized LDL and Lp(a) dose-dependently stimulated renin release. Coincubation with HDL significantly suppressed oxidized LDL and Lp(a) stimulated renin release and O2- production. In MC native and oxidized Lp(a) were poor ligands for the LDL receptor, but bound more tightly to extracellular matrix than native LDL. Native and oxidized Lp(a) elicited proliferation or toxicity of MC in a dose-dependent fashion. Stimulation of DNA synthesis in MC or renin release in JG cells was partly blunted or eliminated when cells were incubated with oxidized LDL and Lp(a) in the presence of superoxide dismutase and catalase, enzymes removing O2- and H2O2. These dat suggest a common underlying mechanism. Atherogenic lipoproteins induce formation of oxygen radicals not only in arteries, but also in glomeruli and JG cells, causing an inhibition of nitric oxide mediated vasodilation, stimulation of renin release, and modulation of mesangial cell growth and proliferation. The damaging effect of the lipoproteins can be prevented by antioxidative enzymes and HDL.
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PMID:Lipids and progression of renal disease: role of modified low density lipoprotein and lipoprotein(a). 940 34

Coronary vascular responses to acetylcholine (ACh, 3 micrograms/kg i.v.), nitroglycerin (NTG, 25 micrograms/kg i.v.), and a 20-s coronary artery occlusion (reactive hyperemia, RH) were investigated in seven conscious dogs with severe left ventricular (LV) hypertrophy and chronic coronary pressure overload (CCPO) due to supravalvular aortic banding and in seven control dogs. All dogs were instrumented for measurement of ultrasonic coronary diameter (CD) and Doppler coronary blood flow (CBF). LV-to-body weight ratio was increased by 82% in CCPO dogs. In control dogs, ACh increased CD (+ 5.9 +/- 1.7%). This response was reduced (P < 0.05) in CCPO dogs (+ 1.9 +/- 0.9%). Similarly, flow-mediated increases in CD after RH were blunted (P < 0.01) in CCPO (+ 2.1 +/- 0.8) vs. control dogs (+ 6.8 +/- 1.8%). In contrast, ACh and RH increased CBF similarly in both groups. Increases in both CD and CBF to NTG were not different between control dogs and CCPO. Peak systolic CBF velocity was greater, P < 0.01, in CCPO (94 +/- 17 cm/s) compared with control (35 +/- 7 cm/s) dogs, most likely secondary to the increased systolic coronary perfusion pressure (215 vs. 130 mmHg). Histological analyses of large coronary arteries in CCPO revealed medial thickening, intimal thickening, and disruption of the internal elastic lamina and endothelium. In contrast, small intramyocardial arterioles failed to show the intimal and endothelial lesions. Thus, in CCPO selective to the coronary arteries, i.e., a model independent from systemic hypertension and enhanced levels of plasma renin activity, endothelial control was impaired for both flow-mediated and receptor-mediated large coronary artery function, which could be accounted for by the major morphological changes in the large coronary arteries sparing the resistance vessels. The mechanism may involve chronically elevated systolic coronary perfusion pressure, CBF velocity, and potential disruption of laminar flow patterns.
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PMID:Selective large coronary endothelial dysfunction in conscious dogs with chronic coronary pressure overload. 948 58

Pharmacological blockade of the renin-angiotensin system in both hypertensive patients and animal models such as the spontaneously hypertensive rat (SHR) effectively reduces blood pressure (BP). Recent studies have established that virally mediated delivery (vector LNSV) of antisense to the angiotensin II type 1 receptor (LNSV-AT1R-AS) will attenuate or abolish the development of hypertension in the SHR. However, the effectiveness of this gene therapy approach to reduce high BP once it is established in the adult has not been ascertained. In this study, we investigated the hypothesis that viral delivery of AT1R-AS into the adult SHR will reduce BP and reverse the vascular reactivity associated with the hypertension. Intracardiac injection of virus particles containing LNSV-AT1R-AS into adult SHR resulted in a 30- to 60-mmHg reduction in BP that was maintained for up to 36 days compared with SHR treated with virus alone (LNSV without antisense). Measurement of renal resistance arteriolar reactivity demonstrated a leftward shift in the KCl and phenylephrine concentration-response relationships and an impaired endothelium-dependent relaxation to ACh in LNSV-treated SHR compared with control Wistar-Kyoto rats. These vascular alterations were reversed in the LNSV-AT1R-AS-treated SHR. Collectively, these data demonstrate that virally mediated gene delivery of AT1R-AS can effectively reduce BP and reverse renovascular pathophysiology associated with the hypertensive state when administered to the adult SHR.
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PMID:Reversal of hypertension by angiotensin II type 1 receptor antisense gene therapy in the adult SHR. 1048 48

The renin-angiotensin (RAS) and the alpha1 sympathetic nervous system (SNS) interact at different levels in cardiovascular regulation. Concurrent use of angiotensin-converting enzyme (ACE) inhibitors and alpha1 receptor antagonists result in a synergistic antihypertensive action and is of wide utility in cardiovascular therapy. We examined the impact of concurrent inhibition of RAS (captopril or losartan) and the SNS (prazosin) before and after acute nitric oxide (NO) synthase inhibition with L-nitro-L-arginine methyl ester (L-NAME) on renal cortical perfusion (RCF) and blood pressure (MAP) in healthy and acute ischemic renal failure (ARF) rats (n = 6). Captopril or losartan reduced MAP and increased RCF more in healthy (p < 0.001) and ARF rats (p < 0.02). Prazosin alone reduced both MAP and RCF (p < 0.001). The combination of prazosin with captopril or losartan caused an additive fall in MAP, and mitigated the fall in RCF. Captopril + prazosin caused a profound fall in RCF following L-NAME, in healthy but not ARF rats (p < 0.001). Acetylcholine (Ach), a vasodilator which stimulates endogenous NO production caused a profound paradoxical fall in RCF in ARF, but not in healthy rats (p < 0.001 ANOVA). These results indicate a significant interaction between angiotensin II and phenylephrine in renal vasomotion. It establishes that endogenous NO homeostatically opposes angiotensin II-alpha1-mediated renal vasoconstriction, and that the vasodilator role of NO is diminished in ARF. The paradoxical fall in RCF induced by Ach in ARF is speculated to result, at least in part, from the formation of peroxynitrite (ONOO-), which acts as a renal vasoconstrictor, following the combination of ischemia-generated super oxide anion (O-2), with endothelial NO released by Ach.
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PMID:Interactions of the renin-angiotensin system and alpha-1 adrenoceptors on renal hemodynamics in healthy and acute renal failure rats: the role of nitric oxide. 1180 63


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