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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Essential hypertension is primarily hereditary. The property inherited is present in all cells but because of adaptation and differentiation it is particularly prominent in systemic vascular smooth muscle. This inherited property is manifested functionally as increased reactivity to vasoactive substances, such as (-)noradrenaline and angiotensin II. This abnormal function is present before the onset of hypertension. Vascular hypertrophy and hyperplasia are not only caused by hyperactivity of the smooth muscle and by the hypertension itself but are also trophic effect of the agonists, especially noradrenaline. The only two proteins in vascular smooth muscle which can produce both contractile and trophic effects are the guanosine triphosphate binding protein (Gs) and phospholipase C. Phospholipase C has already been demonstrated to be abnormally active in response to agonists in the spontaneously hypertensive rat and in human essential hypertension. The Gs protein is less likely to be critically abnormal since it is active in the vascular smooth muscle relaxation cascade as well as in contraction. None of the other proteins involved in vascular smooth muscle contraction or relaxation affect both contractile reactivity and cellular growth. There are many secondary effects dependent upon the phospholipase C abnormality such as calcium (Ca2+) cellular content, Ca2+ Mg2+ ATPase pump effects and possibly Ca2+ Na+ exchange. There are also many secondary effects impinging on the phospholipase C abnormality including changes in noradrenaline and angiotensin II metabolism. Present antihypertensive therapy is directed largely at secondary factors dependent upon or influencing the primary phospholipase C cascade. The path is now open for a more direct and basic diagnostic and therapeutic attack.
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PMID:The aetiology of essential hypertension. 177 Apr 74

In order to define the molecular mechanisms involved in the hypertrophy of the arterial walls observed in essential hypertension, vascular smooth muscle cells were isolated from aortas of spontaneously hypertensive (SHR) and control (WKY) rats, and cultured (until the 4th sub-culture) in the presence of growth factors (foetal calf serum: FCS) and various vasoactive drugs. Growth rate was determined by cell counting and measurement of nuclear thymidine incorporation, and activation of phospholipase C by measurement of the inositol phosphates formed from preincorporated tritiated myo-inositol; the expression of the cellular oncogenes, c-fos and c-myc was visualized by hybridization of Northern blots performed from total RNA. In the presence of low concentrations of FCS (2 p. 100, 5 p. 100) angiotensin II (10(-7)M) and bradykinin (3 X 10(-6)M) increase the growth of both kind of cells. The inositol phosphate formation and the expression of c-fos and c-myc are also dose-dependently stimulated by these vasoactive drugs, and the cultures from SHR are more responsive than those from WKY rats. Phospholipase C hyperreactivity therefore appears to be involved in the increased proliferative ability of vascular smooth muscle cells from SHR. However other molecular processes may be involved, as suggested by the growth inhibition exerted by heparin without any action on PLC activity.
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PMID:[Molecular mechanisms controlling the proliferation of aortic smooth muscle cells in spontaneously hypertensive rats]. 251 Jun 66

Phospholipase C activity governs translocation of Ca2+ from intracellular sites of storage via IP3 (inositol triphosphate) and cell differentiation and growth via DG (diacylglycerol). Phospholipase C responsiveness to various agonists (thrombin, angiotensin II, growth factor) was shown to be increased in various tissues of SHR as compared to WKY (platelets, aortic cultured smooth muscle cells, aortic fibroblasts). The constancy of the response and its physiological significance suggest that this membrane biochemical change plays a crucial role in the pathogenesis of hypertension. Phospholipase C responsiveness was also tested in platelets of untreated hypertensive patients. Half of the sample exhibited an hyperreactivity similar to that observed in SHR rats. This finding confirms the heterogeneity of human essential hypertension and suggests that a proportion of patients have a biological pattern close to that of SHR.
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PMID:[Oncogenes and arterial hypertension]. 267 13

Phospholipase C activity, which influences the control of platelet physiological responses, was investigated in platelets of human essential hypertensives and of spontaneously hypertensive rats (SHR) compared with appropriate normotensive controls, in order to determine whether this enzyme activity could account for the enhanced platelet responses exhibited by hypertensive subjects. After 32P-labelling of cells, the enzyme activity was estimated by measuring the variations in 32P-phosphatidic acid. In resting platelets no difference was observed between hypertensives and normotensives. In contrast, the thrombin-induced increase in 32P-phosphatidic acid in platelets of human hypertensives and of SHR was 30% higher than in controls, suggesting hypersensitivity to phospholipase C in hypertensives. Since, as revealed by phorbol-stimulated phosphorylation of 47-kilodalton protein, intrinsic protein kinase C activity is similar in SHR and controls, our data strengthen the hypothesis than hypersensitivity to phospholipase C influences the hyperreactivity of platelets in primary hypertension.
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PMID:Impaired phospholipase C activity is involved in the hyperreactivity of platelets in primary hypertension. 324 Dec 20