UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Male, homozygous Brattleboro (i.e. vasopressin-deficient) rats were chronically instrumented with pulsed Doppler flow probes and intravascular catheters, and were studied 5 h after a subcutaneous injection of an hyperoncotic solution of polyethylene glycol to render them hypovolaemic, and hence dependent on the renin-angiotensin system for maintenance of haemodynamic status. Pilot experiments showed that, in this model, primed infusion of perindoprilat (0.05 mg kg-1 bolus, 0.05 mg kg-1 h-1 infusion) or captopril (0.2 mg kg-1 bolus, 0.2 mg kg-1 h-1 infusion) just abolished the pressor effect of angiotensin I (120 pmol), and had similar initial hypotensive and renal hyperaemic vasodilator effects. 2. Perindoprilat had more sustained hypotensive, and mesenteric and hindquarters vasodilator effects than captopril in the presence of saline. In the presence of NG-nitro-L-arginine methyl ester (L-NAME 3 mg kg-1 h-1), the renal vasodilator effects of perindoprilat were unchanged, whereas the other haemodynamic effects of perindoprilat and captopril were reduced. Hence, in the presence of L-NAME, all haemodynamic effects of perindoprilat were greater than those of captopril. 3. The renal hyperaemic vasodilator effects of acetylcholine were abolished by L-NAME and by perindoprilat, and were markedly reduced by captopril. However, since perindoprilat and captopril caused such marked renal hyperaemic vasodilatation themselves, it is feasible this change in baseline status contributed to their effects. It is unlikely this could be a full explanation of the results, because the haemodynamic effects of lemakalim were unchanged under any experimental conditions. 4. Bradykinin alone, or in the presence of saline, caused mesenteric hyperaemic vasodilatation whereas, in the presence of perindoprilat or captopril, bradykinin caused marked renal and mesenteric vasoconstrictions. However, in the additional presence of L-NAME, the mesenteric vasoconstriction was reduced, yet the hypotensive effect of bradykinin was augmented. One possible explanation of these observations is that, in the presence of L-NAME and either perindoprilat or captopril, bradykinin caused marked coronary vasoconstriction, leading to a reduction in cardiac output. 5. Neither perindoprilat nor captopril impaired the pressor, or renal, mesenteric, or hindquarters vasoconstrictor effects of L-NAME. Indeed, in their presence, the effects of L-NAME were generally enhanced, consistent with perindoprilat and captopril causing activation of nitric oxide-dependent mechanisms that were subsequently inhibited by L-NAME.
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PMID:Involvement of nitric oxide in the regional haemodynamic effects of perindoprilat and captopril in hypovolaemic Brattleboro rats. 146 39

Inhibition of systemic endothelium-derived relaxing factor (EDRF) synthesis with L-Nw-nitroarginine (L-NAME) results in decreased RBF, which can be reversed by acute blockade of angiotensin II (AII). Because AII is particularly elevated in the renal circulation, it was hypothesized that the degree of renal vasoconstriction produced by L-NAME in Inactin-anesthetized rats is related to PRA. To test this, PRA was chronically increased or suppressed by the manipulation of dietary sodium (eating 0.03% sodium chow or deoxycorticosterone acetate plus drinking 1% NaCl, respectively). After 10 days, rats were anesthetized for determination of blood pressure (BP) and RBF before and after L-NAME (10 mg/kg body wt). In rats with high PRA (61.6 +/- 10.4 ng of angiotensin I [Al]/mL/h; N = 8), L-NAME increased BP by 29 +/- 2 mm Hg (from 110 +/- 4 to 139 +/- 5 mm Hg; P < 0.001), decreased RBF by 27% (from 7.9 +/- 0.3 to 5.8 +/- 0.3 mL/min/g kidney wt; P < 0.001), and increased renal vascular resistance (RVR) by 67% (from 14.5 +/- 0.9 to 24.2 +/- 1.1 resistance units [RU]; P < 0.001). When rats with high PRA (N = 8) were treated with 10 mg/kg body wt of DuP 753, on AII receptor antagonist, L-NAME similarly increased BP by 30 +/- 5 mm Hg (from 81 +/- 3 to 111 +/- 5; P < 0.001) but RBF did not change and RVR increased by only 31% (from 10.9 +/- 0.8 to 13.3 +/- 0.7 RU; P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma renin activity and the renal response to nitric oxide synthesis inhibition. 147 24

Endothelium-derived relaxing factor (EDRF), through its inhibitory second messenger guanosine 3',5'-cyclic monophosphate (cGMP), inhibits renin release in vitro. To determine whether EDRF affects renin in vivo, we tested whether EDRF synthesis inhibition could stimulate renin secretion in intact rats. Because EDRF synthesis inhibition increases blood pressure and consequently withdraws sympathetic activity (both renin inhibitory signals), we also studied the effect of L-N omega-nitroarginine methyl ester (L-NAME) when renal perfusion pressure was controlled and during beta-adrenergic blockade. Mean blood pressure (BP), heart rate (HR), and plasma renin activity (PRA) were measured in anesthetized rats before and after EDRF synthesis inhibition by a 10 mg/kg body wt bolus of L-NAME. L-NAME decreased PRA by 67% [from 11.0 +/- 2.7 to 3.7 +/- 0.8 ng angiotensin I (ANG I).ml-1.h-1, n = 12; P less than 0.001], increased BP by 20 +/- 2 mmHg (P less than 0.001), and decreased HR from 332 +/- 8 to 312 +/- 9 beats/min (P less than 0.005). We repeated our experiment in rats instrumented with an intra-aortic balloon catheter to control renal perfusion pressure and pretreated with propranolol to eliminate the beta-adrenergic effect. Under these conditions, L-NAME now increased PRA by 55% (from 6.9 +/- 1.9 to 10.8 +/- 2.6 ng ANG I.ml-1.h-1, n = 12; P less than 0.02), whereas renal perfusion pressure was unchanged (91 +/- 4 vs. 90 +/- 4 mmHg). HR increased slightly from 308 +/- 5 to 315 +/- 3 beats/min (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelium-derived relaxing factor regulates renin release in vivo. 151 Jan 22

The vascular endothelium plays an essential role in regulating the contractility of the adjacent smooth muscle cell through its secretory and metabolic properties. One of these well known properties is the conversion of angiotensin I into angiotensin II. But the endothelium also secretes at least three compounds able to diffuse to the smooth muscle cell and exerting a paracrine action: these are the prostacyclin (PGI2), the endothelium derived relaxing factor (EDRF) and the endothelin 1. The secretion of these different vasoactive compounds by endothelial cells is triggered by mechanical events, such as the shear stress, or by the effect of several humoral factors locally released, for example from platelets. The compound NO (nitric oxide) is produced by the endothelial enzyme NO synthase from its precursor L-arginine, and is responsible for the vasodilatory and antiplatelets properties of EDRF. NO, by activating the soluble guanylate cyclase in the smooth muscle cell, is responsible for the endothelium dependent vasodilatation. We observed in an isolated perfused rat kidney that the compound L-NAME (NG-monomethyl-L-arginine methyl ester), a competitive inhibitor of NO synthase blocking the production of NO, induces renal vasoconstriction and inhibits renin release. This suggests that not only the renal vasoconstriction but also the renal vasodilatation are active processes, permanently regulated by vasoactive compounds such as EDRF. It seems also that EDRF plays an important role in maintaining the secretion of renin. It can be hypothetized that an abnormality in the release or fate of EDRF might perhaps contribute to high blood pressure, by both a direct effect on the vascular tone and an indirect effect on the release of renin, which in turn regulates also the renal and systemic hemodynamics.
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PMID:[Control of vascular tone by the endothelium: the coupling active vasodilation in the kidney to renin secretion]. 163 4

Preglomerular afferent arteriole (Af-Art) is a crucial vascular segment in the control of glomerular hemodynamics. We have recently reported that vascular reactivity of Af-Art is modulated by nitric oxide (NO). However, little is known about its reactivity under pathophysiological conditions such as diabetes, which is often accompanied by abnormal glomerular hemodynamics. In the present study, we examined the direct effects of high glucose, the hallmark of diabetes, on the vascular reactivity of Af-Art. Rabbit Af-Arts were microperfused for three hours with medium 199 containing either normal (5.5 mM; NG-Af-Arts) or high concentrations (30 mM; HG30-Af-Arts) of glucose, and then vascular reactivity was examined. Sensitivity to angiotensin II (Ang II) was significantly higher in HG30-Af-Arts than in NG-Af-Arts. Ang II began to cause significant constriction from 10(-9) M in NG-Af-Arts (18 +/- 3%, N = 6, P < 0.01) and from 10(-11) M in HG30-Af-Arts (9 +/- 2%, N = 6, P < 0.01). NO synthesis inhibition with 10(-4) M nitro-L-arginine methyl ester (L-NAME) increased the sensitivity to Ang II in NG-Af-Arts without affecting Ang II action in HG30-Af-Arts. In L-NAME-pretreated NG-Af-Arts, Ang II began to cause constriction from 10(-11) M (11 +/- 3%, N = 6, P < 0.01). Thus, pretreatment with L-NAME abolished the difference in sensitivity to Ang II between NG- and HG30-Af-Arts, suggesting impaired NO synthesis in HG30-Af-Arts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High glucose augments angiotensin II action by inhibiting NO synthesis in in vitro microperfused rabbit afferent arterioles. 747 52

Nitric oxide is an important regulator of vascular function and blood pressure. Chronic administration of nitric oxide inhibitors provides a new model of hypertension with pronounced target organ damage. We investigated the effects of oral treatment with N omega-nitro-L-arginine methyl ester (L-NAME) for 6 weeks on vascular reactivity of the aorta in Wistar-Kyoto rats. Certain rats received verapamil or trandolapril in addition to L-NAME. Systolic blood pressure increased in the L-NAME group (by approximately or equal to 80 mm Hg systolic) but not in controls or rats treated with verapamil or trandolapril. Isometric tension changes of aortic rings were recorded. Endothelium-dependent relaxations to acetylcholine were reduced in the L-NAME group (58 +/- 6% versus 104 +/- 1% in placebo, P < .05) but were normalized by treatment with verapamil or trandolapril. In contrast, endothelium-independent relaxations to sodium nitroprusside were not significantly reduced in L-NAME hypertension but were slightly enhanced by trandolapril therapy (P < .05) in the L-NAME group only. In quiescent rings, acetylcholine caused endothelium-dependent contractions in particular after in vitro incubation with L-NAME. These contractions tended to be enhanced in L-NAME hypertension (23 +/- 4% versus 14 +/- 3% in the placebo group; P = NS) and were significantly reduced after treatment with verapamil or trandolapril (P < .05). Concentrations to norepinephrine and angiotensin I and II were unaffected by L-NAME hypertension, whereas those to endothelin-1 were reduced (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:L-NAME hypertension alters endothelial and smooth muscle function in rat aorta. Prevention by trandolapril and verapamil. 759 Oct 13

These studies were performed to determine if the effects of angiotensin II infusion on the development of cardiac fibrosis could be modified by the chronic inhibition of nitric oxide synthase activity. NG-nitro-L-arginine-methyl ester (L-NAME) was administered to adult Wistar rats in drinking water (40 mg/kg per d). Although blood pressure was maintained at hypertensive levels after 2 wk, cardiac hypertrophy or fibrosis did not occur. Angiotensin II, given for 3 d at a dose which induced little or no blood pressure elevation and minimal if any fibrosis, caused significant fibrosis when given to a rat pretreated for 2 wk with L-NAME. This marked fibrosis did not occur if angiotensin II was given shortly after L-NAME treatment was begun or briefly after discontinuation of L-NAME. The fibrosis that occurred with combined treatment was characterized by increased immunodetectable fibronectin, the presence of inflammatory cells within interstitial and perivascular regions, and increased steady state mRNA levels for matrix genes and atrial natriuretic protein. The data indicated a regulatory role for nitric oxide in modulating the angiotensin II-induced cardiac fibrosis and suggest a potentially important autocrine or paracrine role for nitric oxide in fibroblast proliferation.
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PMID:Angiotensin II-induced cardiac fibrosis in the rat is increased by chronic inhibition of nitric oxide synthase. 759 36

Marked neointima formation occurs after balloon injury to the intima of rat arteries. Angiotensin II has been implicated as a growth factor in this process, since angiotensin converting enzyme (ACE) inhibitors block neointima formation after injury. However, ACE is an important kininase, and its inhibitors may act in part by a kinin-mediated mechanism. Kinins are also known to stimulate synthesis of endothelium-derived relaxing factor/nitric oxide (EDRF/NO) and prostacyclin, both of which have antigrowth effects. To determine whether the effect of ACE inhibitors on neointima formation is due to blockade of angiotensin II synthesis alone and/or inhibition of kinin inactivation, we followed two approaches. First, we compared the inhibition of neointima formation induced by the AT1-type angiotensin II receptor antagonist losartan with that caused by the ACE inhibitor ramipril. We also studied whether a kinin receptor antagonist, Hoe 140, blocks the effect of two different ACE inhibitors, ramipril and enalapril, on neointima formation. In addition, we studied whether the effect of ramipril is blocked by an NO synthesis inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME). Although both ramipril and losartan significantly reduced neointima formation, ramipril had a more marked effect (p < 0.05 for ramipril versus losartan). The kinin antagonist Hoe 140 reduced the inhibitory effect of ramipril and enalapril by 73% and 62%, respectively. The remaining effect of the ACE inhibitors was now similar to that of losartan. Inhibition of neointima formation by ramipril was also blocked by the NO synthesis inhibitor L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of kinins and nitric oxide in the effects of angiotensin converting enzyme inhibitors on neointima formation. 768 31

We investigated the role of nitric oxide (NO) in the regulation of migrating motor complex (MMC) cycling during the fasting state and its postprandial disruption. Intravenous infusion of N omega-nitro-L-arginine methyl ester (L-NAME) first produced a premature MMC and then disrupted MMC cycling for the rest of the day. The cycle length of the MMCs was significantly shorter than the control on the 2nd, 3rd, and 4th day after L-NAME infusion. The gastric cyclic motor activity (CMA) did not usually exhibit a premature cycle on the day of L-NAME infusion but was disrupted by L-NAME infusion; the duration of CMA disruption in the stomach was significantly longer than that of MMC disruption in the small intestine. Infusion of N omega-nitro-L-arginine (L-NNA) exhibited similar effects. The intravenous infusion of L-NAME also significantly shortened the duration of MMC disruption by a meal. L-Arginine alone had no significant effect on gastrointestinal motor activity during the fasting or the fed state, but when infused with L-NAME, it blocked the effects of NO synthase inhibition. Angiotensin II increased the mean arterial pressure to a level similar to that produced by L-NAME but had no significant effect on the fasting or the fed pattern of gastrointestinal motor activity. We conclude that NO containing nonadrenergic noncholinergic (NANC) neurons play a significant role in regulating MMC and CMA cycling during the fasting state and their disruption by a meal. However, NO may not be the only NANC neurotransmitter to inhibit contractions in the gut; phase I activity in the small intestine persisted during NO synthase inhibition by L-NAME or L-NNA.
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PMID:Nitric oxide regulates migrating motor complex cycling and its postprandial disruption. 769 78

This study was done to investigate the mechanisms that underly the changes of renal renin gene expression upon hypoperfusion of one kidney. To this end the left renal arteries of male Sprague-Dawley rats were clipped with 0.2 mm silver clips and renal renin mRNA levels were assayed by RNase protection during the first ten days after clipping. Unilateral reduction of renal blood flow led to transient maximal fivefold increases of renin mRNA levels in the clipped kidneys and to sustained suppression of renin gene expression to 20% of the control value in the contralateral intact kidneys. Inhibition of prostaglandin (PG) formation by meclofenamate or EDRF synthesis by L-NAME markedly attenuated the increase of renin mRNA levels in response to clipping, and a combination of PG/EDRF inhibition almost abolished the increase of renin mRNA levels. Inhibition of PG/EDRF formation did not change the suppression of renin mRNA levels in the contralateral intact kidneys. Neither did renal denervation nor inhibition of macula densa function by furosemide prevent the suppression of renin gene expression in response to unilateral renal artery clipping. Only converting enzyme inhibition by ramipril and blockade of Ang II-AT1 receptors by losartan attenuated the decrease of renin mRNA levels in the contralaterals to clipped kidneys. These findings suggest that intact PG and EDRF synthesis represent stimulatory signals for renin gene expression that are required for the elevation of renin mRNA levels upon unilateral renal hypoperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Control of renin gene expression in 2 kidney-1 clip rats. 770

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