Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The data on the characterological personality traits and the vegetative pattern in persons with cerebrovascular pathology (minor brain stroke-MBS) associated with different forms of arterial hypertension (AH) (stable, malignant, labile) make it possible to delineate two psychovegetative personality types. The first one is the hysterical one with an initial sympathetic tone and excess vegetative supply, the second one is the ++anxio-hypochondriac or depressive (more rarely) with an initial parasympathetic or combined vegetative tone with an insufficient level of vegetative supply, and vegetative reactivity. The labile (mild, episodic) forms of AH aggravated by cerebrovascular pathology (MBS) are likely to be the constituent part of the psychovegetative syndrome (the first psychovegetative personality type). The stable forms of AH (including malignant ones) aggravated by episodes of vascular dyscirculatory disorders (MBS) are similar to the second psychovegetative personality type as regards their characterological and vegetative traits. The data obtained can be used not only in subsequent studies of the etiopathogenesis of MBS associated with different forms of AH but also in terms of practical and preventive aspects.
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PMID:[Interrelations between personality characteristics and the autonomic pattern in mild strokes developed in various forms of arterial hypertension]. 166 75

Sex differences in the frequency of physician visits, participation in cancer screening tests, number of drugs consumed, intake of antihypertensive drugs, and participation in hypertension screening have been investigated with data from the Munich Blood Pressure Study I and II (MBS 1981 and 1982). The study population was a random sample of the adult population of Munich (30-69 yrs.). 2216 men and women participated in MBS I (response 69.3%). The results from descriptive analyses and multivariate logistic regression showed significant relationships between sex and the various types of medical care utilization described above, with the exception of participation in hypertension screening, that is participation in the Munich Blood Pressure Study. Also, after controlling for age, marital status, education, occupational position, subjective physical well-being, number of chronic diseases, women went more often to the doctors and consumed more drugs than men. The sex differences were the largest in the participation of cancer screening tests (odds ratio 7.7), and the smallest in the frequency of physician visits (odds ratio 1.8) and participation in hypertension screening (not significant). Additionally, the sex differences in medical care utilization decreased with age.
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PMID:[Sex-specific utilization of medical aid. Results of the Munich Blood Pressure Study]. 326 78

The strength of antihypertensive drug treatment was investigated in a representative sample of the population of Munich. The Munich Blood Pressure Study, a cross-sectional study (MBS I) with follow-up one year later (MBS II) of a random sample of 3,198 citizens aged 30-69 years (response rate 69.3 percent) served as the data base. Using an empirical scale of the relative potency of antihypertensive drugs, the vigor of drug therapy was estimated. One unit of vigor was defined as the equivalent of the recommended average daily dose of the specific drug for long-term treatment. This index of therapeutic vigor was then applied to two groups, treated but uncontrolled hypertensives and controlled hypertensives. We found that 85 percent of the treated uncontrolled hypertensives and 90 percent of those with controlled hypertension were taking only small amounts of medication (less than two units of vigor). Particularly striking was the result that approximately 50 percent of each group received less than one unit of vigor. Based on these data it is concluded that physicians failed to prescribe adequate doses of antihypertensive agents for uncontrolled hypertensives. Furthermore, since a large number of patients had their blood pressure controlled by only very small doses of antihypertensive agents, it may be assumed that at least some of them did not require drug treatment or could have their blood pressure controlled by nonpharmacologic measures alone.
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PMID:The vigor of drug treatment in the control of hypertension: results from the Munich Blood Pressure Study. 387 61

Two mechanisms are proposed to account for the inhibition of myosin phosphatase (MP) involved in Ca2+ sensitization of vascular muscle, ie, phosphorylation of either MYPT1, a target subunit of MP or CPI-17, an inhibitory phosphoprotein. In cultured vascular aorta smooth muscle cells (VSMCs), stimulation with angiotensin II activated RhoA, and this was blocked by pretreatment with 8-bromo-cGMP. VSMCs stimulated by angiotensin II, endothelin-1, or U-46619 significantly increased the phosphorylation levels of both MYPT1 (at Thr696) and CPI-17 (at Thr38). The angiotensin II-induced phosphorylation of MYPT1 was completely blocked by 8-bromo-cGMP or Y-27632 (a Rho-kinase inhibitor), but not by GF109203X (a PKC inhibitor). In contrast, phosphorylation of CPI-17 was inhibited only by GF109203X. Y-27632 dramatically corrected the hypertension in N(omega)-nitro-L-arginine methyl ester (L-NAME)-treated rats, and this hypertension also was sensitive to isosorbide mononitrate. The level of the active form of RhoA was significantly higher in aortas from L-NAME-treated rats. Expression of RhoA, Rho-kinase, MYPT1, CPI-17, and myosin light chain kinase were not significantly different in aortas from L-NAME-treated and control rats. Activation of RhoA without changes in levels of other signaling molecules were observed in three other rat models of hypertension, ie, stroke-prone spontaneously hypertensive rats, renal hypertensive rats, and DOCA-salt rats. These results suggest that independent of the cause of hypertension, a common point in downstream signaling and a critical component of hypertension is activation of RhoA and subsequent activation of Rho-kinase.
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PMID:Activation of RhoA and inhibition of myosin phosphatase as important components in hypertension in vascular smooth muscle. 1260 Aug 88

Regulation of vascular smooth muscle cell contractile state is critical for the maintenance of blood vessel tone. Abnormal vascular smooth muscle cell contractility plays an important role in the pathogenesis of hypertension, blood vessel spasm, and atherosclerosis. Myosin phosphatase, the key enzyme controlling myosin light chain dephosphorylation, regulates smooth muscle cell contraction. Vasoconstrictor and vasodilator pathways inhibit and activate myosin phosphatase, respectively. G-protein-coupled receptor agonists can inhibit myosin phosphatase and cause smooth muscle cell contraction by activating RhoA/Rho kinase, whereas NO/cGMP can activate myosin phosphatase and cause smooth muscle cell relaxation by activation of cGMP-dependent protein kinase. We have used yeast two-hybrid screening to identify a 116-kDa human protein that interacts with both myosin phosphatase and RhoA. This myosin phosphatase-RhoA interacting protein, or M-RIP, is highly homologous to murine p116RIP3, is expressed in vascular smooth muscle, and is localized to actin myofilaments. M-RIP binds directly to the myosin binding subunit of myosin phosphatase in vivo in vascular smooth muscle cells by an interaction between coiled-coil and leucine zipper domains in the two proteins. An adjacent domain of M-RIP directly binds RhoA in a nucleotide-independent manner. M-RIP copurifies with RhoA and Rho kinase, colocalizes on actin stress fibers with RhoA and MBS, and is associated with Rho kinase activity in vascular smooth muscle cells. M-RIP can assemble a complex containing both RhoA and MBS, suggesting that M-RIP may play a role in myosin phosphatase regulation by RhoA.
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PMID:Myosin phosphatase-Rho interacting protein. A new member of the myosin phosphatase complex that directly binds RhoA. 1450 64

Evidence indicates that both the Rho/Rho kinase signaling pathway and reactive oxygen species (ROS) such as superoxide and H(2)O(2) are involved in the pathogenesis of hypertension. This study aimed to determine whether ROS-induced vascular contraction is mediated through activation of Rho/Rho kinase. Rat aortic rings (endothelium denuded) were isolated and placed in organ chambers for measurement of isometric force development. ROS were generated by a xanthine (X)-xanthine oxidase (XO) mixture. The antioxidants tempol (3 mM) and catalase (1,200 U/ml) or the XO inhibitor allopurinol (400 microM) significantly reduced X/XO-induced contraction. A Rho kinase inhibitor, (+)-(R)-trans-4-(1-aminoethyl-N-4-pyridil)cyclohexanecarboxamide dihydrochloride (Y-27632), decreased the contraction in a concentration-dependent manner; however, the Ca(2+)-independent protein kinase C inhibitor rottlerin did not have an effect on X/XO-induced contraction. Phosphorylation of the myosin light chain phosphatase target subunit (MYPT1) was increased by ROS, and preincubation with Y-27632 blocked this increased phosphorylation. Western blotting for cytosolic and membrane-bound fractions of Rho showed that Rho was increased in the membrane fraction by ROS, suggesting activation of Rho. These observations demonstrate that ROS-induced Ca(2+) sensitization is through activation of Rho and a subsequent increase in Rho kinase activity but not Ca(2+)-independent PKC.
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PMID:Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta. 1537 Dec 61

Vascular smooth muscle cells (VSMCs) have a remarkable degree of plasticity and in response to vascular injury, they can change to a dedifferentiated state that can be typically seen in cell cultures. Recently, Y27632, a Rho kinase inhibitor, has been reported to preferentially correct hypertension in a hypertensive rat model. We thus tested the hypothesis that the contraction of the cultured VSMCs might be more dependent on the function of RhoA than the VSMCs in fresh tissue. For this purpose, a tissue-like ring preparation was made using the cultured porcine coronary artery SMCs (CASMCs) and collagen gel (reconstituted ring: R-ring). The R-ring developed an isometric tension on stimulation by high external K+ or various receptor agonists. The phorbol ester (a protein kinase C (PKC) activator)-induced contraction of the intact R-ring was greatly inhibited, while the GTPgammaS (an activator of RhoA)-induced and Ca2+-independent contraction of permeabilized R-ring was greatly enhanced, in comparison to the fresh coronary artery ring. An immunoblot analysis showed the expression levels of RhoA and myosin phosphatase subunits (MYPT1 and PP1cdelta) to be up-regulated, while the levels of CPI-17 (PKC-potentiated protein phosphatase-1 inhibitory protein), h1-calponin and PKC isoforms were downregulated in cultured CASMCs. The knock down of RhoA by RNA interference decreased the contractility of the cultured CASMCs. It is concluded that the contractility of the cultured VSMCs thus appears to be much more dependent on the function of RhoA than VSMCs in fresh tissue. The expression level of RhoA thus plays a crucial role in regulating the contractility of cultured VSMCs.
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PMID:Contractile properties of the cultured vascular smooth muscle cells: the crucial role played by RhoA in the regulation of contractility. 1577 57

Vascular remodeling, rather than vasoconstriction, is believed to account for high vascular resistance in severe pulmonary arterial hypertension (PAH). We have found previously that acute Rho kinase inhibition nearly normalizes PAH in chronically hypoxic rats that have no occlusive neointimal lesions. Here we examined whether Rho kinase-mediated vasoconstriction was also important in a rat model of severe occlusive PAH. Adult rats were exposed to chronic hypoxia ( approximately 10% O(2)) after subcutaneous injection of the vascular endothelial growth factor receptor inhibitor SUGEN 5416. Hemodynamic measurements were made in anesthetized rats after 2 weeks of hypoxia (early group) and 3 weeks of hypoxia plus 2 weeks of normoxia (late group). Both groups developed PAH, with greater severity in the late group. In the early group, intravenous fasudil was more effective than intravenous bradykinin, inhaled NO, or intravenous iloprost in reducing right ventricular systolic pressure. Despite more occlusive vascular lesions, fasudil also markedly reduced right ventricular systolic pressure in late-stage rats. Blood-perfused lungs from late-stage rats showed spontaneous vasoconstriction, which was reversed partially by the endothelin A receptor blocker BQ123 and completely by fasudil or Y-27632. Phosphorylation of MYPT1, a downstream target of Rho kinase, was increased in lungs from both groups of rats, and fasudil (intravenous) reversed the increased phosphorylation in the late group. Thus, in addition to structural occlusion, Rho kinase-mediated vasoconstriction is an important component of severe PAH in SUGEN 5416/hypoxia-exposed rats, and PAH can be significantly reduced in the setting of a severely remodeled lung circulation if an unconventional vasodilator is used.
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PMID:Rho kinase-mediated vasoconstriction is important in severe occlusive pulmonary arterial hypertension in rats. 1733 30

We previously showed that GLUT4 expression is decreased in arterial smooth muscle of deoxycorticosterone acetate (DOCA)-salt hypertensive rats and that GLUT4-knockout mice have enhanced arterial reactivity. Therefore, we hypothesized that increased GLUT4 expression in vascular smooth muscle in vivo would prevent enhanced arterial reactivity and possibly reduce blood pressure in DOCA-salt hypertensive mice. Adult wild-type (WT) and GLUT4 transgenic (TG) mice were subjected to DOCA-salt hypertension with uninephrectomy or underwent uninephrectomy and remained normotensive. GLUT4 expression was increased more than twofold in the aortas of GLUT4 TG mice compared with WT aortas. Eight weeks after implantation of the DOCA pellets, GLUT4 expression decreased by 75% in aortas of WT hypertensive mice, but not in GLUT4 TG hypertensive aortas. Systolic blood pressure was significantly and similarly increased in WT and GLUT4 TG DOCA-salt mice compared with their respective sham-treated controls (159 vs. 111 mmHg). Responsiveness to the contractile agonist 5-HT was significantly increased in aortic rings from WT DOCA-salt mice but remained normal in GLUT4 TG DOCA mice. Phosphorylation of the myosin phosphatase targeting subunit MYPT1 was significantly enhanced in aortas of WT DOCA-salt mice, and this increase was prevented in GLUT4 TG mice. MYPT1 phosphorylation was also increased in nonhypertensive GLUT4-knockout mice. Myosin phosphatase, a major negative regulator of calcium sensitivity, is itself negatively regulated by phosphorylation of MYPT1. Therefore, our results show that preservation of GLUT4 expression prevents enhanced arterial reactivity in hypertension, possibly via effects on myosin phosphatase activity.
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PMID:Preserved expression of GLUT4 prevents enhanced agonist-induced vascular reactivity and MYPT1 phosphorylation in hypertensive mouse aorta. 1736 65

Dramatic and vascular bed-specific hemodynamic changes occur in pregnancy and hypertension of pregnancy (HtP). Because myosin phosphatase (MP) is the primary effector of smooth muscle relaxation and a key target of signaling pathways that regulate vascular tone, we hypothesized that MP expression would be altered in these conditions. The abundance of the targeting/regulatory subunit of MP (MYPT1) mRNA and protein was increased 1.7- to 2.0-fold specifically in the uterine arteries (UAs) of late-pregnant rats without isoform switching. In a model of HtP in which nitric oxide (NO) synthesis is blocked by the chronic administration of N(omega)-nitro-L-arginine methyl ester, MYPT1 was downregulated and switched to the splice variant isoform that codes for the COOH-terminal leucine zipper motif. This was associated with increased sensitivity of the main UA and its subbranches to the vasorelaxant effects of the NO donor drug sodium nitroprusside. This difference was abolished by pretreatment with the phosphatase inhibitor tautomycetin. The sensitivity of relaxation to the NO second messenger cGMP was also increased under calcium-clamp conditions in permeabilized UAs, indicating heightened activation of MP. The changes in MP expression in HtP were largely prevented by treatment with the antihypertensive medicine hydralazine. We propose that MYPT1 isoform switching is an adaptive response to reduce vascular resistance and maintain uterine blood flow in the setting of hypertension-triggered inward remodeling of the UAs in hypertension of pregnancy.
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PMID:Uterine artery myosin phosphatase isoform switching and increased sensitivity to SNP in a rat L-NAME model of hypertension of pregnancy. 1809 48


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