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

To determine whether inhibition of generation of endothelium-derived relaxing factor or nitric oxide (NO) resulted in elevated blood pressure and its effect on resistance arteries, rats were offered NG-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase, in their drinking water. Blood pressure (BP) rose slightly from 100 +/- 2 mmHg in controls to 130 +/- 5 mmHg with 25 mg/Kg L-NAME per day and to 173 +/- 9 mmHg with 100 mg/Kg per day for 2 1/2 to 4 weeks. Rats were studied after 1-2 weeks of hypertension (BP > 150 mmHg). The concentration of cyclic guanosine monophosphate, the intracellular second messenger of NO, was significantly depressed in aorta and in the mesenteric vascular bed in L-NAME-treated rats. Mesenteric resistance arteries studied on a wire-myograph exhibited similar external and lumen diameters, whereas media width and media/lumen ratio were greater (p < 0.01). Cross-sectional area of the media was similar. Active wall tension in response to norepinephrine tended to be greater in blood vessels from L-NAME-treated rats, while responses to vasopressin and endothelin-1 were unaltered. Sensitivity to norepinephrine was significantly enhanced in L-NAME-treated rats (p < 0.001), while that to endothelin-1 and arginine8 vasopressin was similar. In conclusion, administration of an NO synthase inhibitor produces hypertension, with exaggerated media/lumen ratio in resistance arteries and enhancement of response to norepinephrine, which together with decreased NO generation may contribute to elevation of blood pressure.
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PMID:Effect of hypertension induced by nitric oxide synthase inhibition on structure and function of resistance arteries in the rat. 768 50

Subthreshold concentrations of endothelin-1 potentiated the norepinephrine-induced contraction in isometrically mounted rings of the rabbit aorta. Pretreatment with endothelin-1 (0.1 nM) for 10 minutes increased the sensitivity of the aortic rings to norepinephrine without affecting the maximal contraction. This amplification was unaffected by removal of the endothelium but was prevented by the protein kinase C inhibitors staurosporine (0.01 microM) and calphostin C (0.1 microM). Pretreatment of the aortic rings for 24 hours with phorbol 12-myristate 13-acetate (0.1 microM) also abolished the potentiation. Norepinephrine-induced contraction was potentiated by pretreating with phorbol 12-myristate 13-acetate (10 nM) and by increasing the concentration of K+ in the bath solution from 4.6 to 8.6 mM. The potentiation of the norepinephrine-induced contraction by endothelin-1 (0.1 nM) or by phorbol 12-myristate 13-acetate (10 nM) was not associated with an increase in norepinephrine-induced 45Ca2+ uptake or influx, whereas the potentiation due to an increase in the concentration of K+ in the bath solution from 4.6 to 8.6 mM was associated with an increase in norepinephrine-induced 45Ca2+ uptake. We conclude that endothelin-1 potentiation of the norepinephrine-induced contraction occurs in the absence of changes in stimulated Ca2+ entry and is endothelium independent. It is probable that endothelin-1 increases the sensitivity of the contractile apparatus to Ca2+ by activating protein kinase C-dependent mechanisms.
Hypertension 1993 Jul
PMID:Potentiation of norepinephrine-induced contractions by endothelin-1 in the rabbit aorta. 768 34

Resistance arteries may play a critical role in hypertension, and correcting their structural abnormalities may improve the clinical outcome of hypertensive patients. There have been several studies of the effects of antihypertensive treatment on the structure of resistance vessels in hypertension. These studies have yielded inconclusive results regarding the ability of individual drugs to induce regression of the changes occurring in blood vessels in hypertension, both in experimental models and in humans. This article reviews the results of studies of antihypertensive treatment on resistance vessel structure and function, and in particular those of a recent study in which the effects of treatment with the angiotensin-converting enzyme inhibitor cilazapril and the beta-blocker atenolol on the structure and function of subcutaneous resistance arteries were evaluated in a double-blind randomized trial in patients with mild essential hypertension. In this study, patients were randomly assigned to receive either cilazapril or atenolol, and blood pressure was effectively controlled for 1 year. Treatment for 1 year with cilazapril resulted in a significant reduction in the media-to-lumen ratio of resistance arteries dissected from subcutaneous gluteal fat biopsy samples, although the ratio was still slightly but significantly larger than that of resistance arteries of normotensive controls. In arteries from patients treated with atenolol there was no significant change in media-to-lumen ratio with treatment. Contractile responses to several vasoconstrictors, particularly endothelin-1, which were blunted in hypertensive patients, were normalized in the cilazapril-treated patients, but were unchanged in those taking atenolol. These results suggest that in humans it is possible to correct in part the vascular remodeling present in hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of antihypertensive treatment on vascular remodeling in essential hypertensive patients. 770 67

The goal of our studies is to elucidate the role of atrial natrluretic peptide (ANP) and endothelin-1 (ET-1) and their receptor mechanisms in hypoxia-induced pulmonary hypertension and the control of pulmonary artery pressure in patients with pulmonary hypertension. Our experimental model is the male Sprague-Dawley rat subjected to normobaric hypoxia (10% O2, 1 atm) x 4 weeks or less. Our hypothesis is that ET-1 and ANP gene expression are enhanced by exposure to hypoxia and that the ET-1 and ANP so generated have causal and protective, respectively, effects on the development of hypoxia-induced pulmonary hypertension. Results from our studies demonstrated that ANP gene expression and ANP secretion in the heart, and the sensitivity to both endogenous and exogenous ANP in the pulmonary vasculature of hypoxia adapted rats are enhanced during hypoxic exposure. These data defined a role for ANP as a modulator hormone that protects against the development of acute hypoxic pulmonary vasoconstriction and chronic hypoxic pulmonary hypertension. Our studies also demonstrated that ET-1 and endothelin-A receptor (ET-AR) gene expression were selectively enhanced in the pulmonary vasculature by exposure to hypoxia, and that the ET-1 so generated is an important mediator in acute and chronic hypoxia-induced pulmonary hypertension. These results suggest that the intrapulmonary ET-1, acting on ET-AR receptors in the pulmonary vasculature mediates the hypoxia-induced pulmonary vasoconstriction and hypertension. In addition, our recent experiments have demonstrated that administration of BQ-123, a selective ET-AR antagonist, abolished the pulmonary vasoconstrictor response to acute (0-90 min) and chronic (2 weeks) hypoxia, further suggesting that ET-1 plays an important role in the pathogenesis of hypoxia-induced pulmonary hypertension in the rat. Results from our studies also indicate that selective ANP analogs and ET-AR antagonists may be clinically useful for the treatment of pulmonary hypertension.
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PMID:The role of atrial natriuretic peptide and endothelin in hypoxia induced pulmonary hypertension. 770 79

Based on the data from current literature a survey of the new endothelial cell derived peptides endothelins and their characteristics are given. Having the most and longest vasoconstrictor activity that has been described to date and ability to stimulate the release aldosterone, catecholamine and renin, endothelin-1 became the subject of many studies on its pathogenetic role in arterial hypertension. The data also indicate that endothelin may be one of important deleterious mediators in the pathogenesis of ischemic acute renal failure due to its predominant preglomerular vasoconstrictor activity and ability to induce mesangial cells contraction. In addition to its vasoactive properties, endothelin has a mitogenetic and natriuretic effect. The demonstration that mesangial cells release endothelin into culture medium together with the finding that its gene expression and production in mesangial cells are regulated by glomerular inflammatory reaction factors may suggest that endothelin also participates in the complex process of glomerular disease progression. Therefore, it is a very interesting vasoactive peptide, with more actions beyond the regulation of cardiovascular tone, which suggest the widespread distribution of its high activity binding sites in blood vessels, brain, lungs, kidney, adrenal glands, spleen and intestines.
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PMID:[Endothelins]. 771 47

We previously showed that endothelin-1 expression was increased in vascular endothelium of deoxycorticosterone acetate-salt hypertensive rats, whereas in spontaneously hypertensive rats (SHR) it is similar to or less than that in normotensive rats. Treatment with the combined endothelin type A/endothelin type B receptor antagonist bosentan moderately reduced blood pressure rise and nearly completely blunted the development of vascular hypertrophy, particularly in small arteries, in the deoxycorticosterone acetate-salt hypertensive model, suggesting a paracrine role for vascular endothelin-1 in the induction of blood vessel hypertrophy in some forms of experimental hypertension. In the present study we examined the effect of chronic oral treatment for 4 weeks of 12-week-old SHR and Wistar-Kyoto rats (WKY) with 100 mg/kg per day bosentan. Blood pressure rose to hypertensive levels similarly in bosentan-treated and untreated SHR; systolic pressure of WKY was also unaffected. The wet weights of the heart, of aortic segments, and of the mesenteric arterial bed were similar in treated and untreated SHR. When coronary, renal arcuate, mesenteric, and femoral small arteries were evaluated on a wire myograph, the media width and media-to-lumen ratio were greater and the lumen diameter was smaller in vessels from SHR relative to those from WKY, except in small arteries from the renal cortex, in which the lumen was not significantly different in both strains. The media cross-sectional area of small arteries fom the four vascular beds was similar in both strains. Identical morphometric parameters were found in the four vascular beds in bosentan-treated and untreated rats of eh strain.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Apr
PMID:Effect of chronic treatment of adult spontaneously hypertensive rats with an endothelin receptor antagonist. 772 89

We characterized vascular endothelin receptors of the renal artery from adult (12 to 16 weeks of age) and old (72 to 76 weeks) spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Vessels were suspended in organ chambers (37 degrees C, aerated with 95% O2/5% CO2), and isometric tension was recorded. The endothelin-A (ETA) receptor antagonist FR139317, the combined ETA/ETB receptor antagonist bosentan, and the ETB-selective agonist sarafotoxin S6c were used. In old (and less so in adult) SHR, cumulative concentration-contraction curves to endothelin-1 showed a small contraction resistant to FR139317 (10(-5) mol/L) at 3 x 10(-9) to 10(-8) mol/L endothelin-1, which was completely inhibited by bosentan (10(-5) mol/L). This FR139317-resistant contraction to endothelin-1 was not present in WKY. Furthermore, in the presence of FR139317 (10(-5) mol/L), sarafotoxin S6c induced a stronger contraction in old SHR than in WKY (P < .05). In rings contracted with norepinephrine, sarafotoxin S6c caused endothelium-dependent relaxations in both strains; these relaxations were blocked by N omega-nitro-L-arginine methyl ester, indicating that nitric oxide is the mediator. In WKY but not SHR, release of nitric oxide by sarafotoxin S6c increased with age (P < .05). Thus, both ETA and ETB receptors mediate contraction to endothelin-1 in the renal artery from SHR but not WKY. ETB receptors on vascular smooth muscle seem to be unmasked with age in SHR, whereas those on endothelium (mediating nitric oxide release) exhibit more efficient responses with age in WKY.
Hypertension 1995 Apr
PMID:ETA and ETB receptors mediate contraction to endothelin-1 in renal artery of aging SHR. Effects of FR139317 and bosentan. 772 90

We investigated the possible relationship between endothelin-1 injection into the dorsolateral periaqueductal gray area and the glutamatergic system in the control of cardiovascular function. Endothelin-1 was injected into the dorsolateral periaqueductal gray area of freely moving rats at doses ranging from 0.1 to 10 pmol. Endothelin-1 increased arterial blood pressure (from 7.0 +/- 1.6 to 55.0 +/- 4.1 mm Hg, mean +/- SEM) in a dose-dependent manner and induced characteristic behavioral changes such as longitudinal rolling of the body (barrel-rolling). DL-2-Amino-5-phosphonovaleric acid and (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[D-alpha] cyclohepten-5,10-imine hydrogen maleate, both selective N-methyl-D-aspartate excitatory amino acid receptor antagonists, but not 6-cyano-7-nitroquinoxaline-2,3-dione, a non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, significantly decreased endothelin-1-induced cardiovascular and behavioral changes (P < .01). Prazosin and propranolol, adrenergic blocking agents, and reserpine, a depletor of catecholamine stores, also prevented these effects. We propose that the glutamatergic system may exert, via N-methyl-D-aspartate receptors, a significant influence on endothelin-1-induced cardiovascular and behavioral effects after its injection into the periaqueductal area.
Hypertension 1995 Apr
PMID:Endothelin-1 in rat periaqueductal gray area induces hypertension via glutamatergic receptors. 772 91

Endothelin-1 infusion into humans to obtain pathophysiological plasma levels causes mild hypertension, strong renal vasoconstriction, and sodium retention. We studied whether oral use of the angiotensin-converting enzyme inhibitor enalapril (20 mg BID) or the calcium channel blocker nifedipine (60 mg OD) could attenuate these effects of endothelin-1 (2.5 ng/kg per minute for 90 minutes) in six healthy volunteers. Endothelin infusion alone increased plasma endothelin from 3.0 +/- 0.3 to 8.8 +/- 1.0 pmol/L (P < .05). Blood pressure rose by approximately 6 mm Hg (P < .05). Renal function changes were relatively large: Renal blood flow decreased from 941 +/- 76 to 729 +/- 118 mL/min (P < .05) and glomerular filtration rate from 105 +/- 9 to 92 +/- 10 mL/min (P < .05); renal vascular resistance increased from 101 +/- 7 to 152 +/- 20 mm Hg.min/L (P < .05); and sodium excretion decreased from 158 +/- 54 to 86 +/- 27 mumol/min (P < .05). Enalapril treatment reduced blood pressure from 94 +/- 2 to 87 +/- 3 mm Hg (P < .05) and prevented the hypertensive response to endothelin. By contrast, despite renal predilatation, endothelin reduced renal blood flow strongly (from 1063 +/- 127 to 763 +/- 100 mL/min, P < .05), although maximal renal vascular resistance was numerically lower (124 +/- 11 mm Hg.min/L) than during endothelin alone (P < .05). Glomerular filtration rate fell from 118 +/- 11 to 108 +/- 11 mL/min (P < .05). Enalapril did not alter the antinatriuretic effect of endothelin.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Apr
PMID:Effectiveness of enalapril versus nifedipine to antagonize blood pressure and the renal response to endothelin in humans. 772 6

To define the molecular mechanisms of endothelin-1 (ET-1) gene regulation, we cloned, sequenced, and characterized the rat ET-1 promoter. A sequence consisting of the first 1329 bp of the rat ET-1 promoter was investigated in greater detail. Sequence analysis identified putative binding sites for a number of transcriptional factors that may be involved in ET-1 gene regulation. Several of these factors have been proposed earlier to be involved in cell-specific gene regulation and may be responsible for directing ET-1 expression in vivo. For functional analysis of the ET-1 promoter, we generated a reporter gene construct using luciferase as reporter gene under control of the promoter fragment isolated. The construct was transfected transiently into bovine aortic endothelial cells, and luciferase expression was evaluated. The results indicated that the promoter segment used showed high expression in endothelial cells comparable to that induced by viral promoters. Since ET-1 is regulated by a number of vasoactive substances, we studied the effect of angiotensin II on endothelin transcription. We could demonstrate a dose-dependent transcriptional activation of ET-1 transcription by angiotensin.
Hypertension 1995 Apr
PMID:Characterization and functional analysis of the rat endothelin-1 promoter. 772 16


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