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

The objective of this study was to examine the effects of long-term antihypertensive therapy on blood pressure and vascular responses of resistance arteries during prolonged inhibition of nitric oxide synthesis. Four groups of 6-week-old Wistar-Kyoto rats were treated with either placebo as controls or N omega-nitro-L-arginine methyl ester (L-NAME) alone or in combination with verapamil or with trandolapril. Drugs were given orally for 6 weeks or short-term in vitro to vessels obtained from untreated rats. Endothelium-dependent and -independent relaxations as well as contractions were studied in isolated perfused mesenteric and renal arteries with an arteriograph. Kidney nitric oxide synthase activity was also evaluated. Verapamil and trandolapril prevented the increase in systolic blood pressure and the blunted acetylcholine-induced relaxations that occurred with L-NAME treatment without improving the nitric oxide synthase activity. Both antihypertensive regimens also normalized sensitivity to sodium nitroprusside, which was enhanced by L-NAME. In contrast, short-term in vitro preincubation with verapamil or trandolaprilat in the presence of L-NAME did not improve the impaired relaxations to acetylcholine. Long-term but not short-term therapy with a calcium antagonist or angiotensin-converting enzyme inhibitor improved the blunted endothelium-dependent relaxations in nitric oxide-deficient hypertension. These findings strongly suggest that the role of other vasodilator systems, which normally do not regulate vascular tone, is enhanced with long-term but not short-term treatment with these drugs. These observations emphasize the potential importance of these treatments in the management of hypertension in which nitric oxide production is diminished.
Hypertension 1996 Jan
PMID:Antihypertensive therapy prevents endothelial dysfunction in chronic nitric oxide deficiency. Effect of verapamil and trandolapril. 859 83

Inhibition of nitric oxide synthase by L-arginine analogues is associated with elevation of blood pressure in rats. Deoxycorticosterone acetate (DOCA)-salt hypertensive rats and DOCA-salt-treated spontaneously hypertensive rats (SHR) overexpress the endothelin-1 gene in blood vessels, and this is associated with severe vascular hypertrophy, whereas SHR do not overexpress endothelin-1 and exhibit limited vascular hypertrophy. In this study malignant hypertension was induced in SHR by chronic administration of the L-arginine analogue NG-nitro-L-arginine methyl ester (L-NAME), a potent inhibitor of nitric oxide synthase, to determine whether malignant hypertension would result in endothelin-1 gene overexpression in blood vessels and in greater severity of vascular hypertrophy, as found in malignant DOCA-salt-treated SHR. L-NAME treatment induced malignant hypertension in SHR, with a systolic blood pressure of 246 +/- 2 mm Hg, compared with 211 +/- 2 mm Hg (P < .01) in untreated SHR. Plasma renin activity was very high in L-NAME-treated SHR, and their plasma immunoreactive endothelin concentration was slightly but significantly elevated (P < .01). After 3 weeks of treatment, aortic and to a lesser degree mesenteric artery weights were significantly increased in L-NAME-treated SHR compared with untreated SHR. However, cardiac weight and the media cross-sectional area or media width-to-lumen diameter ratio of small arteries from the coronary, renal, mesenteric, or femoral vasculature were not increased in L-NAME-treated SHR in comparison with untreated SHR. The abundance of endothelin-1 mRNA measured by Northern blot analysis was significantly increased in L-NAME-treated SHR in aorta and with less magnitude in the mesenteric arterial tree. The absence of accentuation of cardiac and small artery hypertrophy in malignant hypertension in L-NAME-treated SHR, despite enhanced expression of the endothelin-1 gene in blood vessels, may suggest a direct or indirect inhibitory effect of L-NAME on cardiovascular growth, probably independent of its effects on nitric oxide synthase, counterbalanced in aorta and large mesenteric arteries by the hypertrophic effect of enhanced vascular endothelin-1 gene expression. These results also suggest a role for blood pressure and potentially for nitric oxide in the regulation of endothelin-1 gene expression in blood vessels.
Hypertension 1996 Jan
PMID:Vascular structure and expression of endothelin-1 gene in L-NAME-treated spontaneously hypertensive rats. 859 87

The effect of the chronic oral application of NG-nitro-L-arginine methyl ester (L-NAME), a potent inhibitor of nitric oxide (NO) production, was studied on hypothalamic blood flow (HBF) and hypothalamic nitric oxide synthase (NOS) activity in rats. L-NAME was dissolved in the drinking water, in a concentration of 0.1 mg/ml, and was administered for 1 week. In the chronic L-NAME pretreated animals significantly reduced hypothalamic NOS activity and marked hypothalamic vasoconstriction were observed, the latter of which was counteracted by sustained systemic arterial hypertension, while HBF remained unchanged. The present model of chronic NOS blockade may be useful to assess the physiological functions of NO in the regulation of cerebral blood flow in the normally perfused brain.
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PMID:Hypothalamic blood flow remains unaltered following chronic nitric oxide synthase blockade in rats. 859 37

We used Ro 46-8443, non-peptidic antagonist selective of endothelin ETB receptors, to study the role of ETB receptors in rat hypertension models. In normotensive rats, Ro 46-8443 decreased blood pressure, but in SHR and DOCA rats, it induced a pressor effect, due to blockade of ETB-mediated release of nitric oxide since L-NAME prevented it. In rats rendered hypertensive by chronic L-NAME, Ro 46-8443 did not induce a pressor but depressor effect. Thus, in DOCA rats and SHR, Ro 46-8443 reveals a predominant influence of endothelial 'vasorelaxant' ETB receptors, while in normotensive rats the prevailing role of ETB receptors seems to be in mediating a vasoconstrictor tone.
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PMID:The role of ETB receptors in normotensive and hypertensive rats as revealed by the non-peptide selective ETB receptor antagonist Ro 46-8443. 861 87

Recent studies suggest that enhanced renal sympathetic nervous activity plays an important role in mediating the renal hemodynamic and electrolyte excretion changes associated with acute inhibition of NO synthesis. The purpose of this study was to determine the importance of renal nerves in mediating the long-term hypertensive and renal actions of NO synthesis blockade. To achieve this goal, we infused N(G)-nitro-L-arginine methyl ester (L-NAME) at a rate of 25 microg/kg per minute for 2 weeks in control dogs and in bilaterally renal-denervated dogs. NO synthesis blockade in control dogs increased arterial pressure by 18%, from 94 +/- 3 to 111 +/- 4 mm Hg, and decreased heart rate from 74 +/- 4 to 57 +/- 4 beats per minute (bpm). L-NAME also decreased renal plasma flow from 195 +/- 18 to 166 +/- 18 mL/min while having no effect on glomerular filtration rate (67 +/- 7 versus 63 +/- 6 mL/min). In the renal-denervated dogs, inhibition of NO synthesis increased arterial pressure by 14%, from 92 +/- 4 to 105 +/- 5 mm Hg, and decreased heart rate from 80 +/- 4 to 65 +/- 5 bpm. Renal plasma flow in this group decreased from 195 +/- 20 to 165 +/- 20 mL/min, whereas glomerular filtration rate remained unchanged (66+/- 6 versus 64 +/- 6 mL/min). In addition, renal excretion of sodium and water in response to L-NAME was similar in each group. The results of this study indicate that the long-term hypertensive and renal effects of NO synthesis inhibition in the dog are not dependent on activation of the renal sympathetic nervous system.
Hypertension 1996 Mar
PMID:Role of renal nerves in mediating the hypertensive effects of nitric oxide synthesis inhibition. 861 12

After secretion by the heart, atrial natriuretic factor (ANF) circulates in plasma, whereas C-type natriuretic peptide (CNP), which is found in abundance in the endothelium, may regulate vascular tone in a paracrine manner. However, there is little information on the effect of CNP on renal microvessels. We hypothesized that CNP dilates the afferent arteriole via the nitric oxide pathway, whereas ANF acts directly on vascular smooth muscle cells. When we perfused rat kidneys with minimal essential medium and bovine serum albumin at 100 mm Hg and examined the juxtamedullary afferent arterioles, neither CNP nor ANF was found to have any effect. When the peptides were added to arterioles preconstricted with norepinephrine, CNP and ANF dilated them in a similar fashion; diameters increased by 25 +/- 4% (n=7) and 29 +/- 6% (n=6) at 10(-7) mol/L, respectively (P < .008). Pretreatment with 10(-4) mol/L N-nitro-L-arginine methyl ester (L-NAME) or 5 x 10(-6) mol/L indomethacin blocked CNP-induced dilation; dilation by ANF was unaffected by indomethacin (52 +/- 25%, n=5) and potentiated by L-NAME (73 +/- 14%, n=5). Thus, CNP dilates the afferent arterioles via the prostaglandin/nitric oxide pathway, whereas ANF dilates them directly. This difference may be important in controlling glomerular hemodynamics.
Hypertension 1996 Mar
PMID:Mechanisms of action of atrial natriuretic factor and C-type natriuretic peptide. 861 25

The influence of nitric oxide (NO) on basal vascular tone varies with different hypertensive models or vascular beds. The goal of the present study was to examine the role of NO in the maintenance of resting cerebral blood flow (CBF) during chronic hypertension. In 9-10 months old Wistar-Kyoto (WKY) rats (n=47) and spontaneously hypertensive rats (SHR;n=47) anesthetized with pentobarbital sodium (60 mg/kg i.p.), regional CBF of the right parietal cortex was monitored by laser-Doppler flowmetry. Reductions in CBF in response to intravenous infusion of the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 1, 3, 10, and 30 mg/kg) were similar between WKY rats (17 +/- 6 approximately 43 +/- 6%; means +/- SE) and SHR (15 +/- 6 approximately 48 +/- 6%) while arterial blood pressure was maintained on the baseline level by controlled hemorrhage. Effects of L-NAME (3 mg/kg i.v.) on arterial blood pressure and CBF were almost completely inhibited by L-arginine (300 mg/kg i.v.), but not by D-arginine (300 mg/kg i.v.). In addition, intravenous infusion of L-arginine (300 mg/kg) alone did not affect resting CBF in both WKY rats and SHR. Thus, these findings suggest that 1) NO plays an important role in the maintenance of resting CBF in both normotensive and chronically hypertensive rats and 2) the contribution of NO to the maintenance of resting CBF is not altered during chronic hypertension.
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PMID:Role of nitric oxide in the maintenance of resting cerebral blood flow during chronic hypertension. 861 76

Long-term nitric oxide blockade by N omega -nitro-L-arginine methyl ester (L-NAME) leads to severe and progressive hypertension. The role of salt intake in this model is unclear. To verify whether salt dependence in this model is related to the extent of nitric oxide inhibition, we gave adult male Munich-Wistar rats a low salt, standard salt, or high salt diet and oral L-NAME treatment at either 3 or 25 mg/kg per day. At 10 to 15 days of treatment, the slope of the pressure-natriuresis line was decreased in rats receiving low-dose L-NAME compared with untreated controls. In rats treated with the higher dose, the line was shifted to the right but remained parallel to that obtained in untreated controls. Renal vascular resistance was moderately increased in rats receiving low-dose L-NAME, whereas high-dose L-NAME induced a marked vasoconstriction that was aggravated by salt overload. Low-dose L-NAME treatment induced hypertension only when associated with sodium overload. In rats receiving high-dose L-NAME, hypertension was aggravated by sodium excess but was not ameliorated by sodium restriction. Long-term (6 weeks) L-NAME treatment was associated with progressive hypertension, which was aggravated by salt overload, and with the development of albuminuria, focal glomerular collapse, glomerulosclerosis, and renal interstitial expansion. These abnormalities were worsened by salt overload and largely prevented by salt restriction. In the model of chronic nitric oxide blockade, salt dependence is a function of the inhibitor dose, and renal injury varies directly with the level of salt intake.
Hypertension 1996 May
PMID:Effect of salt intake and inhibitor dose on arterial hypertension and renal injury induced by chronic nitric oxide blockade. 862 Dec 12

Short-term infusions of angiotensin II (Ang II) increase renal vascular resistance and thereby endothelial shear stress and nitric oxide (NO) release. Prolonged stimulation of Ang II can decrease the expression of NO synthase isoforms in the macula densa, but prolonged increases in shear stress can increase transcription of endothelial NO synthase. Therefore, we designed these studies to test the hypothesis that Ang II exerts time-dependent effects on renal NO generation as assessed from renal excretion of nitrate and nitrite, percent increases in renal vascular resistance during inhibition of NO synthase with intravenous NG -nitro-L-arginine methyl ester (L-NAME), or decreases in renal vascular resistance during stimulation of endothelial NO synthase with intravenous acetylcholine. Rats were tested during graded short-term (30 to 90 minutes intravenous) or prolonged (5 to 6 days subcutaneous) Ang II infusions that led to dose-dependent increases in blood pressure and renal vascular resistance and reductions in renal blood flow. Captopril was administered for 3 to 4 days to suppress Ang II generation. The renal excretion of nitrate and nitrite was increased during short-term Ang II infusions (from 205 +/- 22 to 331 +/- 58 pmol.min-1, P < .05) but was unchanged during prolonged Ang II infusion (control group, 197 +/- 33 versus Ang II, 245 +/- 42 pmol.min-1, P=NS). The percent increase in renal vascular resistance with L-NAME was potentiated dose dependently by short-term but not long-term Ang II infusions. The increase in renal vascular resistance with L-NAME in control rats without Ang II infusions was +150 +/- 13%. At an Ang II infusion of 200 ng.kg-1.min-1, the L-NAME-induced percent increase in renal vascular resistance was significantly (P < .01) increased compared with controls in short-term Ang II-infused rats (+369 +/- 70%) but was not significantly different in prolonged infused rats (+190 +/- 33%). Intravenous acetylcholine caused dose-dependent renal vasodilation that was not significantly changed in rats receiving short-term intravenous Ang II but was significantly (P < .005) potentiated in those receiving prolonged Ang II infusions (change in renal vascular resistance with acetylcholine at 10 micrograms.kg-1.min-1 versus control, -21.5 +/- 5.0%; with short-term Ang II, -24.9 +/- 4.5%; with long-term Ang II, -52.1 +/- 7.2%). In conclusion, short- and long-term Ang II infusions caused equivalent changes in blood pressure and renal blood flow and hence presumably equivalent increases in endothelial shear stress. However, only short-term Ang II infusions increased NO generation and the dependence of the renal circulation on NO, whereas acetylcholine-induced NO release was enhanced selectively during long-term Ang II infusions. This suggests that during long-term Ang II, renal NO release may become uncoupled from shear stress yet remains highly responsive to receptor-mediated stimulation.
Hypertension 1996 May
PMID:Role of nitric oxide in short-term and prolonged effects of angiotensin II on renal hemodynamics. 862 Dec 13

In rats, chronic administration of the nitric oxide (NO) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) causes arterial hypertension, cardiac hypertrophy and myocardial ischemic alterations such as necrosis and fibrosis. In this study, we evaluated the effect of 8 weeks of treatment with enalapril maleate on cardiac weight and on the development of the histological alterations induced by L-NAME. Enalapril significantly inhibited the development of both arterial hypertension (117.2 +/- 5.8, 161.8 +/- 8.8 and 122.0 +/- 10.6 mm Hg, for control, L-NAME- and L-NAME + enalapril-treated animals, respectively) and left ventricular hypertrophy (1.36 +/- 0.13, 1.60 +/- 0.04 and 1.48 +/- 0.05 mg/g, for control, L-NAME- and L-NAME + enalapril-treated animals, respectively), but had no effect on the myocardial lesions. These findings demonstrate that although the renin-angiotensin system plays a major role in the development of arterial hypertension and cardiac hypertrophy, it does not modulate the ischemia-induced myocardial alterations observed in this model.
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PMID:Enalapril does not prevent the myocardial ischemia caused by the chronic inhibition of nitric oxide synthesis. 866 33


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