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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) is a tonically produced vasodilator that maintains blood pressure (BP) in the normal animal. In these studies, we produced chronic NO blockade by oral administration of the NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME), which produced sustained hypertension and increased renal vascular resistance (RVR) in conscious rats. Acute blockade of the angiotensin II type 1 (AT1) receptor with losartan had little effect on BP and RVR in either chronically NO-blocked or normal conscious rats. Acute blockade of the alpha 1-adrenoceptor with prazosin produced moderate similar falls in BP in both chronically NO-blocked and normal rats. The combination of AT1 and alpha 1-adrenoceptor blockade was profoundly antihypertensive and was particularly effective in lowering BP in chronically NO-blocked rats where the hypertension was obliterated. In contrast, the increased RVR persisted in chronically NO-blocked rats receiving combined acute AT1 and alpha 1-adrenoceptor blockade. These observations indicate that, in the sustained phase of chronic NO blockade, the hypertension is largely due to the combined activities of alpha 1-adrenoceptor and AT1 stimulation.
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PMID:Angiotensin II and alpha 1-adrenergic tone in chronic nitric oxide blockade-induced hypertension. 820 22

The aim of this study was to assess regional haemodynamic changes in conscious Brattleboro rats during chronic ingestion of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). Animals were instrumented with renal, mesenteric and hindquarters pulsed Doppler flow probes and an intra-arterial catheter, and haemodynamic measurements were made before, during and after 14 days' exposure to L-NAME (0.01 mg ml-1 in the drinking water). Within 6 h after addition of L-NAME to the drinking water, mean arterial blood pressure was increased (maximum, 33 +/- 6 mm Hg), and remained so until L-NAME was withdrawn, whereupon blood pressure returned to normal levels within 24 h. The hypertension was accompanied by a transient reduction in mesenteric blood flow, and a more persistent reduction in hindquarters blood flow. Mesenteric and, particularly, hindquarters vascular conductance showed a sustained reduction. However, during ingestion of L-NAME, renal blood flow was not diminished and, over the final 4 days of exposure to L-NAME there was no significant renal vasoconstriction. All regional haemodynamic effects of L-NAME were lost within 24 h of its withdrawal. Hence, as with shorter periods of exposure to the less potent NO synthase inhibitor, NG-monomethyl-L-arginine, the hypertension caused by L-NAME is dependent on its continued administration, and is associated with a particularly marked hindquarters vasoconstriction.
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PMID:Regional haemodynamics in Brattleboro rats during chronic ingestion of NG-nitro-L-arginine methyl ester. 820 18

Cerebral blood flow and glucose utilization were measured in rat neocortex, using [14C]iodoantipyrine and 2-deoxy-D-[14C]glucose quantitative autoradiography, respectively, following nitric oxide synthesis inhibition with L-NAME. In intact animals cortical blood flow was decreased, despite increased arterial blood pressure above autoregulatory limits, whilst glucose use remained unaffected. Unilateral sympathectomy at the superior cervical ganglion had no effect, suggesting that the autoregulatory response to L-NAME-induced hypertension is independent of sympathetic activity.
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PMID:Sympathetic denervation and the cerebrovascular response to hypertension induced by NG-nitro-L-arginine methyl ester. 820 83

We contrasted in normotensive and hypertensive rats the effect of inhibition of nitric oxide synthesis on isometric tension development by aortic rings bathed in Krebs' bicarbonate buffer. NG-Nitro-L-arginine methyl ester (L-NAME) (3 x 10(-4) mol/L) increased tension (82 +/- 11% of the response to 120 mmol/L potassium chloride) in rings of thoracic aorta taken from hypertensive rats 7 to 14 days after aortic coarctation, whereas rings of abdominal aorta from below the coarctation were unresponsive, as were rings of thoracic aorta from rats with deoxycorticosterone-salt-induced hypertension and from the corresponding normotensive controls of either model of hypertension. The contractile response to L-NAME in aortic rings of rats with aortic coarctation was reversed by L-arginine (1 mmol/L), attenuated by removal of the endothelium, and blunted by the protein kinase C inhibitor staurosporine but was unaffected by inhibition of cyclooxygenase, scavengers of superoxide anion, or blockade of receptors for angiotensin, norepinephrine, serotonin, or endothelin. In additional experiments we contrasted the effect of L-NAME (10 mg/kg IV) on the blood pressure of sham-operated rats and rats with aortic coarctation after pretreatment of animals in both groups with DuP 753 (30 mg/kg IV) to achieve blood pressure equalization. The pressor response to L-NAME was twofold greater in rats with aortic coarctation than in sham-operated controls. That pressor and aortic constrictor responsiveness to L-NAME are increased after aortic coarctation suggests that a mechanism of vasodilation, mediated by nitric oxide, is preferentially manifested in rats with aortic coarctation-induced hypertension.
Hypertension 1994 Jun
PMID:Vascular responsiveness to nitric oxide synthesis inhibition in hypertensive rats. 820 72

The roles of the sympathetic nervous system, angiotensin II, and arginine vasopressin in the cardiovascular-renal responses to nitric oxide synthesis inhibition were examined in eight conscious dogs equipped with arterial and venous catheters and a nonoccluding bladder catheter. Nitric oxide inhibition was achieved by intravenous infusion of NG-nitro-L-arginine methyl ester (L-NAME) at 37.1 nmol/kg per minute for 140 minutes in the control group. The same dogs, after a 1-week recovery, were pretreated for 2 days with either prazosin for alpha 1 blockade, prazosin plus propranolol for alpha 1 plus beta blockade, L-158,809 for angiotensin receptor blockade, or d(CH2)Tyr(Me)arginine vasopressin for vasopressin-V1 blockade, and the L-NAME infusion was repeated. After 140 minutes of L-NAME infusion into the control group, mean arterial pressure and renal vascular resistance had increased 16% and 71%, and renal blood flow, glomerular filtration rate, urine flow, and urinary sodium excretion had decreased 33%, 16%, 61%, and 64%, respectively. The decrement in renal blood flow and glomerular filtration during L-NAME administration was unaffected by any of the neurohumoral blockers. During V1 blockade L-NAME resulted in only a 3% increase in arterial pressure, attenuation of the renal vascular resistance response, and almost total elimination of the decrease in urine flow. During angiotensin blockade the L-NAME-induced increase in arterial pressure was markedly attenuated, and the decrease in urinary sodium excretion was attenuated in the alpha 1 plus beta blockade group.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 Jun
PMID:Mechanisms involved in the cardiovascular-renal actions of nitric oxide inhibition. 820 34

Exposure to noxious environmental stimuli such as air-jet stress (AJS) produces a pattern of hemodynamic changes referred to as the "defense reaction". In the rat these changes include a relatively modest increase in mean arterial blood pressure (MAP), tachycardia, renal and mesenteric vasoconstriction, and a marked hindquarter vasodilation. The aim of the present study was to determine whether the AJS-induced decrease in hindquarter resistance is mediated by a sympathetic neurogenic vasodilator system that uses nitric oxide (NO) and/or related nitrosyl factors. AJS produced a small, rapid increase in MAP, which quickly returned to baseline (within 5 seconds), and a substantial increase in hindquarter blood flow and decrease in hindquarter resistance, which occurred almost instantaneously (1 to 2 seconds) and were sustained for at least 30 seconds. The intravenous injection of either bretylium (5 mg/kg), which prevents impulse propagation-mediated release of neurotransmitters/neuromodulators from sympathetic terminals, or NG-nitro-L-arginine methyl ester (L-NAME, 25 mumol/kg), which blocks NO synthesis, essentially abolished the AJS-induced increase in hindquarter blood flow and fall in hindquarter resistance. In contrast, the hindquarter vasodilation produced by the NO donor sodium nitroprusside (4 micrograms/kg i.v.) was markedly exaggerated in the bretylium- or L-NAME-treated rats. We also found that rat lumbar sympathetic fibers projecting to the hindquarter vasculature contain NADPH diaphorase, a marker for NO synthase in paraformaldehyde-perfused tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 Jun
PMID:Nitrosyl factors mediate active neurogenic hindquarter vasodilation in the conscious rat. 820 36

Recent studies have indicated that chronic administration of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, produces marked hypertension. Although the mechanism of this form of hypertension is not well understood, several studies have demonstrated that sympathetic nerve activity is at least acutely elevated after L-NAME administration. To evaluate the potential role of the renal sympathetic nerves in L-NAME-induced hypertension, we compared the blood pressure response to L-NAME in four groups of Sprague-Dawley rats (n = 8 each): (1) sham-operated vehicle-treated, (2) sham-operated L-NAME-treated, (3) denervated vehicle-treated, and (4) denervated L-NAME-treated. After renal denervation or sham surgery, L-NAME was added to the drinking water (70 mg/100 mL) for 4 weeks, and arterial pressure was measured weekly by the tail-cuff method. L-NAME treatment caused a progressive increase in arterial pressure in sham-operated rats, rising to 154 +/- 6 mm Hg by week 4 of treatment compared with 115 +/- 2 mm Hg in the vehicle-treated sham-operated group (P < .005). In contrast, the development of hypertension was significantly delayed and attenuated in renal-denervated rats treated with L-NAME. The results of our study suggest that L-NAME-induced hypertension may be partly mediated by or is at least dependent on the integrity of the renal nerves.
Hypertension 1994 Jun
PMID:Hypertension induced by nitric oxide synthesis inhibition is renal nerve dependent. 820 37

Bradykinin-induced relaxation of precontracted, porcine coronary artery (PCA) rings is mediated by distinctly different endothelium-derived relaxing factors depending on the contractile agent used. Thus when contracted with KCl, bradykinin-induced relaxation of PCA rings is mediated solely by nitric oxide (NO), whereas when contracted with the thromboxane mimetic U46619, a small component of the relaxation is attributable to NO and a large component is attributable to a non-NO mechanism that is independent of cyclooxygenase activity. We hypothesized that the non-NO component was mediated by arachidonic acid (AA) or by a non-cyclooxygenase product of AA metabolism. Bradykinin-induced relaxations of PCA rings precontracted with U46619 in the presence of indomethacin (10 mumol/L) were moderately attenuated by the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 100 mumol/L), whereas when precontracted with KCl, L-NAME abolished the relaxations. AA produced endothelium-dependent relaxations of rings precontracted with U46619 that were unaffected by L-NAME, whereas AA did not relax rings precontracted with KCl. In rings precontracted with U46619, in the presence of L-NAME and indomethacin the phospholipase inhibitors quinacrine (50 mumol/L) and 4-bromophenacyl bromide (10 mumol/L) attenuated bradykinin- but not AA-induced relaxations. Inhibitors of both lipoxygenase (BW 755c [100 mumol/L] and nafazatrom [20 mumol/L]) and cytochrome P-450 (proadifen [10 mumol/L] and clotrimazole [10 mumol/L]) pathways did not eliminate bradykinin- or AA-induced relaxations, although clotrimazole partially attenuated AA-induced relaxations. These findings suggest that bradykinin-induced relaxation of PCA rings is mediated by AA through a mechanism that is not dependent on cyclooxygenase, lipoxygenase, or cytochrome P-450 pathways.
Hypertension 1994 Jun
PMID:Relaxation of porcine coronary artery to bradykinin. Role of arachidonic acid. 820 38

Blood pressure elevations after nitric oxide inhibition may result in part from increased sympathetic tone. In this study arterial baroreceptor reflex control of heart rate, renal sympathetic nerve activity (RSNA), and adrenal sympathetic nerve activity (ASNA) were compared in rats given normal tap water or a 3.7 nmol/L (10 mg%) solution of NG-nitro-L-arginine methyl ester (L-NAME) for 1 or 5 weeks. L-NAME raised blood pressure after 5 weeks of treatment (153 +/- 3 versus 130 +/- 3 and 124 +/- 2 mm Hg, 5 weeks versus 1 week and control). The sensitivity of arterial baroreceptor reflex control of RSNA was reduced after both 1 and 5 weeks of treatment (-5.05 +/- 0.63% and -4.46 +/- 0.2% versus -6.43 +/- 0.39% baseline activity per millimeters of mercury). Set point gain of ASNA was attenuated after 5 weeks of treatment compared with controls (-1.7 +/- 3% versus -3.3 +/- 3% baseline activity per millimeters of mercury). Maximal inhibition of ASNA was attenuated in groups treated 1 and 5 weeks (60 +/- 3% and 66 +/- 3% versus 34 +/- 4% baseline activity). The maximal increase in both RSNA and ASNA was elevated in rats treated 5 weeks (RSNA: control, 263 +/- 19%; 1 week, 224 +/- 17%; 5 weeks, 324 +/- 20%; ASNA: control, 272 +/- 29%; 1 week, 252 +/- 31%; 5 weeks, 361 +/- 28% baseline activity). The data indicate that chronic L-NAME treatment alters arterial baroreceptor reflexes in part before the onset of hypertension.
Hypertension 1994 Jun
PMID:Sympathetic baroreceptor responses after chronic NG-nitro-L-arginine methyl ester treatment in conscious rats. 820 39

The effects of the nitric oxide synthesis inhibitor NG-nitro-L-arginine methylester (L-NAME) on mean arterial blood pressure (MABP) and local cerebral blood flow were determined in conscious and halothane-anaesthetised rats. Thirty minutes post-drug administration in conscious rats L-NAME (30 mg kg-1 i.v.) induced significant hypertension (MABP 132 +/- 2 mmHg and 163 +/- 6 mmHg (means +/- S.D.) for saline and L-NAME groups respectively) and significant hypoperfusion throughout the brain (mean +/- S.D. reduction in cerebral blood flow 27.3 +/- 5.9% compared with controls). In contrast, under halothane anaesthesia, L-NAME did not significantly change MABP but significant reductions in cerebral blood flow (43.2 +/- 3.7%) were observed. Thus the cerebrovascular response to L-NAME is conserved under halothane anaesthesia despite attenuation of the peripheral vasoconstrictive action.
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PMID:Cerebrovascular effects of NG-nitro-L-arginine methylester are conserved under halothane anaesthesia. 828 21


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