Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A deficiency of nitric oxide may be responsible for the increased vascular resistance associated with human essential hypertension and that seen in animal models of hypertension. Premenopausal females are relatively protected from hypertension and cardiovascular complications. Levels of superoxide can influence the availability of nitric oxide. We hypothesize that there are differences in nitric oxide availability between stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) and that superoxide may be responsible for at least some of these differences. We studied vascular reactivity in endothelium-intact aortic rings from WKY and SHRSP. We measured nitric oxide synthase activity in endothelial cells removed from aortas and also measured circulating nitrite/nitrate levels. We found the response to N(G)-nitro-L-arginine methyl ester to be significantly greater in WKY compared with SHRSP (95% CI: 20 to 174; P=.015) and in females compared with males in WKY (95% CI: 143 to 333; P=.00004) and SHRSP (95% CI: 70 to 224; P=.0006). Endothelial nitric oxide synthase activity was significantly greater in SHRSP compared with WKY (95% CI: 2.3 to 17.6; P=.016). The EC50 for relaxation to carbachol was significantly greater in male rats compared with female rats (95% CI: -1.1 to -0.2; P=.003) within the SHRSP strain. The maximum relaxation to carbachol was significantly attenuated in stroke prone spontaneously hypertensive compared with Wistar-Kyoto rats (95% CI: 1.7 to 14.4; P=.015). Diethyldithiocarbamate had a significantly greater effect on the stroke prone spontaneously hypertensive rats' carbachol response than that of Wistar-Kyoto rats (95% CI: 14.3 to 47.0; P=.0008). We conclude that superoxide may be responsible for strain differences in vascular reactivity, whereas nitric oxide availability may be responsible for sex differences independently of endothelial nitric oxide synthase activity and superoxide.
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PMID:Sex differences in the abundance of endothelial nitric oxide in a model of genetic hypertension. 940 76

Endothelial nitric oxide synthase (eNOS), encoded by NOS3, is a potent regulator of vasomotor tone and peripheral resistance. Congenic experiments indicate that a chromosomal segment containing the rat eNOS gene contributes to rat spontaneous hypertension (HT). A role for NOS3 in onset of essential hypertension (HT) is, however, controversial. We therefore decided to test NOS3 polymorphisms in a set of patients who have an accentuated ability to show an existing genetic association. The 112 HT subjects had two HT parents and the normotensive (NT) subjects had two NT parents. All were Anglo-Celtic whites. The two most promising polymorphisms, viz, a biallelic variable number of tandem repeats (VNTR) in intron 4 and an exon 7 variant that leads to an amino acid change (Glu298Asp), were genotyped by PCR (and BanII digestion in the case of the latter). Frequency of the minor allele of the VNTR was 0.11 in the NT and 0.10 in the HT subjects (P = .9). For the exon 7 variant, Asp298 frequency was 0.30 and 0.32 in each respective group (P = .6). Tracking was seen for the Asp298 allele with elevation in body mass index (P = .034), and the minor allele of the VNTR with elevation in LDL (P = .007) and reduction in HDL (P = .048). In conclusion, we saw no association of NOS3 markers with HT in the population studied. However, possible genotypic effects on plasma lipids and body mass index might warrant further studies, especially in view of possible associations with heart disease.
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PMID:Association analyses of endothelial nitric oxide synthase gene polymorphisms in essential hypertension. 1098 49

Endothelial nitric oxide synthase (eNOS) serves a number of functions in the vasculature. In response to stimuli such as shear stress or acetylcholine, eNOS catalyses the production of nitric oxide (NO) from L-arginine. The NO diffuses across the endothelium into neighbouring smooth muscle and induces vasodilation. NO also acts locally to prevent platelet and leucocyte aggregation and inhibits vascular smooth muscle cell proliferation. It has been shown that mice lacking eNOS have decreased blood pressure, decreased heart rate and increased plasma renin activity. It has also been reported that NO production was reduced in patients with essential hypertension compared with normotensive individuals. In several animal models of renal disease (subtotal renal ablation, ureteral obstruction and diabetes), the administration of L-arginine, and probably the increase in NO synthesis, reduced the degree of glomerulosclerosis, ameliorated the changes in the tubulointerstitial compartment of the kidney and also decreased the infiltration of the kidney by invading macrophages. In summary, the L-arginine-NO pathway plays an important role in hypertension, renal disease, inflammation and atherosclerosis. This pathway also interacts with the renin-angiotensin system, the eicosanoid pathway, endothelin, cytokines and regulators of inflammation such as NF-kappaB.
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PMID:The role of nitric oxide in hypertension and renal disease progression. 1136 23

Endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO) which, after diffusing into vascular smooth muscle cells, activates guanylate cyclase leading to vasodilatation. A polymorphism (894G to T) in exon 7 of the eNOS gene causes the conversion of Glu to Asp in position 298. The recently described crystal structure of the heme domain of eNOS protein shows that Glu298 is fully solvent accessible and distant from regions integral to enzyme function. Searching for phenotypic expression of eNOS gene variants, we genotyped a group of patients with essential hypertension (H, n = 119) for the Glu298Asp polymorphism and compared them with age- and sex-matched healthy normals (N, n = 85). To specify phenotypic expression further, the hypertensive patients were subdivided into one group that responded well to regular antihypertensive therapy (CH, n = 45) and one group that was resistant to the therapy (RH, n = 74). Patients with BP higher than 140/90 mmHg when on adequate lifestyle modification and triple-combination therapy (including diuretics) were considered resistant. In RH and H groups, a significantly higher frequency of T alleles (P = 0.022 and P = 0.046, respectively) was found compared to normotonics (N). In well-controlled hypertonics, the same tendency was found, but did not reach statistical significance. The Glu298Asp polymorphism may contribute to the complex pathogenesis of essential hypertension and may be a factor in the resistance of these patients to conventional antihypertensive therapy. The presence of this allele may thus be predictive of the patients' therapeutic response.
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PMID:Association of the Glu298Asp polymorphism in the endothelial nitric oxide synthase gene with essential hypertension resistant to conventional therapy. 1139 96

We review recent and ongoing work from our laboratory that has shed novel insights into the effects of angiotensin II (ANGII) on the baroreflex at the level of the nucleus of the solitary tract (NTS). The NTS is the site of termination for baroreceptor afferents and is a potentially powerful region for neuronal modulation. ANGII applied to this nucleus attenuated the cardiac vagal and cardiac sympathetic components of the baroreceptor reflex. This effect was antagonized by blockade of either gamma-amino butyric acid receptors or nitric oxide synthase within the NTS. Interestingly, nitric oxide donors microinjected into the NTS mimicked the effect of ANGII. Using an adenovirus we showed that ANGII activated the endothelial isoform of nitric oxide synthase. The NTS was transfected to express a dominant negative truncated mutant form of endothelial nitric oxide synthase that prevented the depressant effect of ANGII on the baroreflex. Endothelial nitric oxide synthase was present in both neurones and endothelium in the NTS. A possibility is that ANGII activation of endothelial nitric oxide synthase is calcium dependent. However, in most NTS neurones tested, ANGII failed to elevate intracellular calcium concentration. We conclude that ANGII activates endothelial nitric oxide synthase to release nitric oxide which enhances gamma-amino butyric acid transmission destined for circuitry mediating the baroreflex. We discuss the contribution of endothelial cells within the nucleus of the solitary tract as a potential target for both circulating and/or centrally produced ANGII. These data have relevance to patients with essential hypertension and left heart failure, conditions in which ANGII activity is elevated and the baroreceptor reflex is depressed.
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PMID:Unravelling mechanisms of action of angiotensin II on cardiorespiratory function using in vivo gene transfer. 1167 35

Vascular endothelial cells produce nitric oxide (NO), which contributes to the regulation of blood pressure and regional blood flow. Endothelial nitric oxide synthase (eNOS) gene polymorphisms are associated with coronary artery disease, but their linkage with primary hypertension is controversial. A total of 103 individuals with primary hypertension and 104 normotensive control subjects were studied in Singapore. The specific genotypes for G894T missense variant in exon 7, variable number tandem repeats (VNTR) in intron 4 (eNOS 4A/B/C) and T-786C in the promoter were isolated using allele-specific gene amplification and restriction fragment length polymorphism to examine the association of genotype and allelic frequency in both groups. Logistic regression analysis was also used to detect the association between genotypes and hypertension. Five genotypes of intron 4 VNTR (AA, AB, BB, AC and BC) were observed. Intron 4 B/B genotype was significantly associated with the hypertension group (P = 0.035), but disequilibrium of G894T and T-786C was absent between the two groups (P = 0.419 and P = 0.227), respectively. The overall distribution of allelic frequency differed significantly between the two groups, with four-repeat allele (4A) of intron 4 more frequent in the normotensive group than the hypertensive group (P = 0.019). Logistic regression analysis showed that intron 4 B/B genotype was significantly associated with systolic blood pressure of individuals with body mass index greater than 25 kg/m2 (P = 0.04). In conclusion, the eNOS 4 B/B genotype is a genetic susceptibility factor for primary hypertension in a Singapore population.
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PMID:Association analysis of endothelial nitric oxide synthase gene polymorphism with primary hypertension in a Singapore population. 1702 34