Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00627 (MAP)
 15,705 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of inhibiting endogenous nitric oxide (NO) synthesis with NG-monomethyl-L-arginine (L-NMMA) on the systemic and splanchnic circulation have been investigated in rats with experimental chronic portal hypertension, anaesthetized with ketamine. 2. Portal hypertension was induced by partial portal vein ligation, 2 weeks prior to study. This procedure induced a reduction in systemic arterial blood pressure (MAP), an increase in cardiac output as measured by radiolabelled microspheres, a reduction in peripheral and splanchnic vascular resistance and an increased portal venous inflow (PVI) and portal pressure, as compared to control non-ligated rats. 3. L-NMAA (6.25 and 50 mg kg-1, i.v.) dose-dependently increased MAP, reduced cardiac output and PVI, and increased peripheral and splanchnic vascular resistance. With L-NMMA (50 mg kg-1), PVI and the vascular resistances returned to values comparable to those determined in control non-ligated anaesthetized rats under resting conditions. 4. Porto-collateral resistance was also increased by these doses of L-NMMA, whereas portal pressure was unchanged. The increase in renal blood flow and decrease in renal vascular resistance also seen in portal-hypertensive rats was reversed by L-NMMA (50 mg kg-1). 5. These effects of L-NMMA (50 mg kg-1) were inhibited by prior administration of L-arginine (300 mg kg-1, i.v.). 6. These findings indicate that the chronic hyperdynamic circulatory characteristics following portal vein stenosis can be attenuated by L-NMMA. Thus, the excessive formation of endogenous NO may be implicated in the pathogenesis of the haemodynamic disturbances and splanchnic vasodilatation associated with chronic portal hypertension.
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PMID:Effects of inhibiting nitric oxide biosynthesis on the systemic and splanchnic circulation of rats with portal hypertension. 159 80

Since dietary salt loading enhances nitric oxide (NO) generation in the kidney, we investigated the hypothesis that changes in salt intake have specific effects on vascular resistance in the kidney mediated by the L-arginine-NO pathway. We contrasted changes in renal and hindquarter vascular resistances (RVR and HQVR) in anesthetized rats during intravenous infusions of graded doses of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Groups (N = 8 to 10) of rats were maintained on a high salt (HS) or low salt (LS) diet for two weeks. Compared to those on LS, rats on HS had a greater increase in mean arterial pressure (delta MAP; +32 +/- 4 vs. +22 +/- 3%; P = 0.05) and RVR (+160 +/- 17 vs. +83 +/- 10%; P < 0.005) and a greater fall in renal blood flow (delta RBF; -47 +/- 3 vs. -32 +/- 4%; P < 0.01); changes in HQVR were similar in the two groups. The enhanced RVR response to L-NAME in HS rats could not be ascribed to the higher renal perfusion pressure (RPP) since it persisted in rats whose RPP was controlled by adjustment of a suprarenal aortic clamp. Changes in RVR with an NO donor (SIN-1) were similar in HS and LS rats. L-NAME reduced plasma renin activity in both HS and LS rats. After inhibition of ACE with captopril, or of angiotensin II type I (AT1) receptor with losartan, the increase in RVR with L-NAME remained greater in HS than LS rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal vasoconstriction during inhibition of NO synthase: effects of dietary salt. 752 72

7-Nitro indazole (7-NI) inhibits mouse cerebellar nitric oxide synthase (NOS) in vitro with an IC50 of 0.47 microM. Following i.p. administration in mice, 7-NI (10-50 mg kg-1) produces dose-related anti-nociception as evidenced by an inhibition of late phase (15-30 min) but not early phase (0-5 min) hindpaw licking time following subplantar injection of formalin (10 microliters, 5% v/v). The ED50 for this effect was 26 mg kg-1 (equivalent to 159.5 mumol kg-1). Similar i.p. administration of 7-NI (20 and 80 mg kg-1) in urethane-anaesthetized mice failed to increase MAP. Thus, 7-NI is a novel inhibitor of NOS which exhibits selectivity for the brain enzyme. Accordingly, 7-NI may be a useful starting point for the development of selective, centrally acting NOS inhibitors devoid of cardiovascular side effects and as a tool to study the central pharmacological effects of nitric oxide (NO).
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PMID:7-Nitro indazole, an inhibitor of nitric oxide synthase, exhibits anti-nociceptive activity in the mouse without increasing blood pressure. 768 May 91

Over the past decade, the survival rate of infants with congenital diaphragmatic hernia (CDH) treated in the intensive care unit of the Royal Children's Hospital, Melbourne, has remained unchanged at 56% +/- 6%. Newer forms of treatment, such as extracorporeal membrane oxygenation (ECMO), high-frequency oscillation, and surfactant and nitric oxide therapy, are now available. The exact role of these therapies in the management of infants with CDH has not been determined. This study examines five clinical parameters derived from an infant's best preoperative ventilatory and blood gas data in the first 24 hours of life. One hundred twenty-five CDH infants were admitted to the intensive care unit between January 1, 1981 and December 31, 1991. Criteria for inclusion in the study were (1) CDH diagnosed within 6 hours of delivery, (2) ventilation before repair, and (3) no associated lethal congenital abnormality. Of the 90 cases studied in detail, there were 38 deaths (42% mortality rate). All five parameters were analyzed by receiver operating curve analysis to determine the optimum value of each parameter in predicting survival. An oxygenation index (MAP x FIO2/PaO2) of less than 0.08 predicted a 94% chance of survival, with a sensitivity of 96% and a specificity of 95%. Similarly, a modified ventilation index (PIP x RR x CO2/1,000) of less than 40 predicted a 91% chance of survival, with a sensitivity of 94% and a specificity of 86%. By stratifying each criterion according to outcome, three groups of infants were identified according to their response to conventional therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Predictors of survival for infants with congenital diaphragmatic hernia. 784 17

The in vitro vasorelaxant and in vivo cardiovascular effects of synthetic S-nitrosothiols (RSNOs) were compared to standard nitrovasodilators. S-Nitroso-glutathione (GSNO), S-nitroso-N-acetylcysteine (NACysNO), S-nitroso-galactopyranose (GPSNO), S-nitroso-thioglycerol (TGSNO) and S-nitroso-homocysteine (HCysNO) relaxed phenylephrine (PE) contracted rabbit aorta at 50% effective concentrations (EC50s) of 3-46 nM. While nitroglycerin (GTN) exhibited in vitro tolerance after preincubation, the RSNOs were considerably less cross tolerant to GTN. In conscious dogs, GSNO, NACysNO and GPSNO (1-20 mcg/kg/min i.v.) paralleled nitroprusside (SNP) in reducing mean arterial and central venous pressure (MAP; CVP) with mild tachycardia. GSNO, NACysNO and SNP were more hypotensive and more resistant to isosorbide dinitrate (ISDN) cross tolerance than GTN. NACysNO showed mild self tolerance with low infusion (2.5 mcg/kg/min x 4h x 3 days) and blunted GTN's hypotension. These studies demonstrate that GSNO and NACysNO are SNP-like vasodilators in conscious dogs, which exhibit less cross tolerance to ISDN than GTN. Further, RSNOs relax vascular smooth muscle seemingly independent of nitric oxide (NO) liberation, and nitrate tolerance may involve reduced RSNO formation or NO release rather than desensitized guanylate cyclase (GC).
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PMID:In vitro vasorelaxant and in vivo cardiovascular effects of S-nitrosothiols: comparison to and cross tolerance with standard nitrovasodilators. 793 11

In order to find out whether the pressor effect of arginine vasopressin (AVP) is limited by release of nitric oxide (NO) and whether it is altered in hypertension, blood pressure (MAP) and heart rate (HR) responses to i.v. administration of AVP were compared in conscious normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats under control conditions and during blockade of NO synthesis induced by i.v. administration of NG-nitro-L-arginine (L-NOARG). In control experiments AVP elicited significant elevations of MAP in WKY and SHR. The maximum increases in WKY and SHR amounted 26 +/- 3 and 16 +/- 3 mmHg, respectively, and did not differ significantly from each other. In WKY increase of MAP was associated with significant bradycardia. Administration of AVP in this strain during blockade of NO synthesis resulted in significantly smaller increase of blood pressure (13 +/- 5 mmHg) than under control conditions (p < 0.001), and in nonsignificant changes of HR. In SHR AVP caused a progressive significant decrease of blood pressure associated with transient tachycardia. The results indicate that blockade of NO synthesis does not enhance but reduces increase of blood pressure in WKY and transforms the pressor action of this peptide into the hypotensive effect in SHR. This phenomenon is discussed in relevance to the possible unfavorable effects of AVP on coronary and/or cerebral circulation during blockade of NO formation.
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PMID:Effect of NG-nitro-L-arginine on pressor action of arginine vasopressin in normotensive (WKY) and spontaneously hypertensive (SHR) rats. 794 33

To compare the contribution of nitric oxide (NO) to the buffering of short-term and circadian fluctuations of arterial blood pressure with that of the baroreceptor reflex, conscious foxhounds were subjected to continuous 24-h blood pressure recordings. A pressure transducer was placed into the lumen of the abdominal aorta. Telemetry recordings were done under control conditions, following blockade of NO formation by intravenous bolus injection of NG-nitro-L-arginine (L-NNA; 16.5 +/- 2 mg/kg body wt) and after total sinoaortic and cardiopulmonary denervation in five dogs each. L-NNA produced a sustained elevation of mean arterial pressure (MAP; 137.2 +/- 6.4 mmHg vs. control, 112.9 +/- 3.7 mmHg). After denervation, no significant increase of MAP was found (113.5 +/- 4.1 mmHg), but the standard deviation of the MAP histogram was significantly greater (22.5 +/- 3.1 vs. 10.6 +/- 0.9 mmHg, P < 0.05). Sequential spectral analysis showed that total power between 0 and 0.5 Hz was elevated more than twofold after L-NNA (P < 0.05). This was due primarily to increased power in the range above 0.1 Hz. After denervation, total power increased about three-fold (P < 0.05), almost exclusively occurring below 0.04 Hz. Power in the range above 0.2 Hz was diminished, although not significantly. It is concluded that in the conscious dog, NO, as well as the baroreceptor reflex, is an effective blood pressure buffer. NO is most effective above 0.1 Hz, whereas the baroreceptors primarily buffer fluctuations slower than 0.04 Hz.
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PMID:The blood pressure buffering capacity of nitric oxide by comparison to the baroreceptor reflex. 806 5

In up to 60% of women with chronic renal disease an elevation of blood pressure is seen during pregnancy. The pathogenesis of this complication may be related to a diminished synthesis of vasodilatory substances by endothelial cells and to an increased sensitivity to vasopressor hormones such as angiotensin II. Previous experimental studies in rats with early chronic renal disease (adriamycin nephropathy, AN) have shown that this pregnancy-induced hypertension is associated with a lowered synthesis of glomerular PGE2. In the present study the vascular response to vasoactive substances was evaluated. In AN rats the sensitivity to an acute infusion of angiotensin II was augmented, whilst it was blunted in normal pregnant rats. Chronic treatment with the thromboxane-(Tx)-receptor antagonist, daltroban (60 mg/kg/day, p.o.) administered from mid-pregnancy induced a similar reduction in blood pressure in both AN virgin and pregnant rats. This suggests that adriamycin per se may induce vascular damage which may interfere with the normal vascular adaptation to pregnancy. Stimulation of NO synthesis with L-arginine decreased MAP values significantly in PAN rats but did not modify them during normal pregnancy. In additional experimental inhibition of the endothelial-derived relaxing factor (EDRF), nitric oxide (NO) synthesis with NAME from mid-pregnancy significantly increased SBP and MAP in normal rats. By contrast, in PAN rats chronic NAME treatment had no effect. In summary, the development of hypertension in pregnant rats with AN may be associated to endothelial cell dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pregnancy-induced hypertension in rats with early adriamycin nephropathy. 807 19

Competitive inhibition of the conversion of L-arginine to nitric oxide by a high dose of NG-monomethyl-L-arginine (L-NMMA) leads to significant increases in arterial pressure, natriuresis, and diuresis in Sprague-Dawley rats. The purpose of this study was to determine the extent of the natriuretic and diuretic responses and the possible role of arterial pressure and renal interstitial hydrostatic pressure (RIHP) elevations with the infusion of L-NMMA in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Intravenous infusion of L-NMMA (15 mg/kg bolus followed by 500 micrograms.kg-1.min-1 continuous infusion) in WKY rats (n = 8) resulted in a significant increase in mean arterial pressure (MAP, 122 +/- 3 to 152 +/- 2 mmHg), RIHP (4.7 +/- 0.4 to 6.7 +/- 0.5 mmHg), fractional excretion of sodium (FENa, 0.76 +/- 0.21 to 4.74 +/- 0.70%), and urine flow rate (V, 27.7 +/- 5.0 to 161.3 +/- 19.6 microliters/min). Increases in RIHP and sodium and water excretions are abolished when renal perfusion pressure is prevented from increasing with L-NMMA infusion in a group of WKY rats (n = 6). In SHR (n = 6) administration of the same dose of L-NMMA resulted in no significant changes in MAP (172 +/- 3 to 178 +/- 2 mmHg) or RIHP (3.3 +/- 0.4 to 3.5 +/- 0.6 mmHg), but significantly higher increases in FENa (1.19 +/- 0.26 to 7.52 +/- 0.68%) and V (47.1 +/- 10.0 to 248.3 +/- 25.7 microliters/min) compared with WKY rat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of nitric oxide causes exaggerated natriuresis in spontaneously hypertensive rats. 820 60

The renal blood flow (RBF) of patients with polycythemia rubra vera is increased despite the high hematocrit (Hct) which elevates the whole blood viscosity. Since blood viscosity determines the shear force on the endothelium which is a major stimulus to nitric oxide (NO) release, we investigated the hypothesis that renal vasodilation during erythropoietin-induced erythrocytosis is mediated by the L-arginine-NO pathway. Groups of Sprague-Dawley rats received thrice weekly injections of erythropoietin (E) for two to five weeks; responses were contrasted with normal rats (N) which received sham injections. The first group was studied after five weeks of erythropoietin injections which led to sharp increases in Hct (E: 72 +/- 3 vs. N: 44 +/- 1%) and mean arterial pressure (MAP: 126 +/- 3 vs. 107 +/- 3 mm Hg). These rats had an elevated basal RBF whether measured by the clearance and renal extraction of PAH or by a transit-time renal blood flow meter. Subsequent groups were studied after two to three weeks of erythropoietin which raised the Hct more modestly to 59 +/- 2%. In this group, the basal MAP was similar in E and N rats. Graded doses of the NO synthase inhibitor, N omega-monomethyl-L-arginine (L-NMA) led to a steeper rise in MAP in E than N; at the highest doses, the MAP had increased by 36 +/- 2 in E and 23 +/- 3 mm Hg in N (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide mediates renal vasodilation during erythropoietin-induced polycythemia. 837 85


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