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

In order to test the hypothesis that the activity of cardiovascular centres is determined by their content of cAMP a number of drugs which influence the activity of either phosphodiestase or adenylcyclase were injected in doses of 100-1000 mug/kg into the lateral cerebral ventricle of cats. The effects on blood pressure and heart rate were studied. The phosphodiesterase inhibitors papaverine, carbocromene, theophylline and caffeine caused hypertension and tachycardia which increased with the dose while the phosphodiesterase activator imidazole exerted opposite effects. Sodium fluoride which activates adenylcyclase increased blood pressure and heart rate substantially. The results confirm the above-mentioned hypothesis.
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PMID:Further evidence for the involvement of cAMP in central blood pressure regulation. 18 30

Immunohistochemical distributions of tyrosine hydroxylase and calmodulin in the rat forebrain were analyzed quantitatively as a possible model for the hypertension mechanism. The brain slices of spontaneously hypertensive rats (SHR) at 12 weeks of age were stained immunohistochemically for tyrosine hydroxylase and for calmodulin, and the distributions and amounts of these proteins were measured at 40-microns intervals by a fluorescence microphotometry system in comparison with those in normotensive control, Wistar Kyoto rats (WKY, the parent strain of SHR). Tyrosine hydroxylase levels in the neostriatum, nucleus accumbens, nucleus septi lateralis and tractus diagonalis, and calmodulin levels in the medial part of the neostriatum of SHR were lower than those in WKY. We reported previously that the decrease of the serum calcium level in SHR causes a decrease of the dopamine levels in the neostriatum and nucleus accumbens regions through a calmodulin-dependent system, and subsequent low levels of dopamine in the brain which may produce an increase in blood pressure. Combining this finding and our previous reports, we also suggest that the lower dopamine levels seen in the neostriatum and nucleus accumbens regions of SHR may result from the decrease in tyrosine hydroxylase and/or calmodulin levels in these regions in addition to the abnormality of calcium metabolism, and low levels of dopamine may produce an increase in blood pressure through functions of cerebral dopaminergic neurons and peripheral sympathetic nerves.
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PMID:Quantitative immunohistochemical distributions of tyrosine hydroxylase and calmodulin in the brains of spontaneously hypertensive rats. 136 39

The primary mechanism of regulation of smooth muscle contraction involves the phosphorylation of myosin catalyzed by Ca2+/calmodulin-dependent myosin light chain kinase. However, additional mechanisms, both Ca(2+)-dependent and Ca(2+)-independent, can modulate the contractile state of smooth muscle. Protein kinase C was first implicated in the regulation of smooth muscle contraction with the observation that phorbol esters induce slowly developing, sustained contractions. Protein kinase C occurs in at least four Ca(2+)-dependent (alpha, beta I, beta II, and gamma) and four Ca(2+)-independent (delta, epsilon, zeta, and eta) isoenzymes. Only the alpha, beta, epsilon, and zeta isoenzymes have been identified in smooth muscle. Both classes of isoenzymes have been implicated in the regulation of smooth muscle contraction. However, the physiologically important protein substrates of protein kinase C have not yet been identified. Specific isoenzymes may be activated by different contractile agonists, and individual isoenzymes exhibit some degree of substrate specificity. Prolonged activation of protein kinase C can result in its proteolysis to the constitutively active catalytic fragment protein kinase M, which would dissociate from the sarcolemma and phosphorylate proteins such as myosin that are inaccessible to membrane-bound protein kinase C. Protein kinase M induces relaxation of demembranated smooth muscle fibers contracted at submaximal Ca2+ concentrations. We suggest that protein kinase C plays two distinct roles in regulating smooth muscle contractility. Stimuli triggering phosphoinositide turnover or phosphatidylcholine hydrolysis induce translocation of protein kinase C (probably specific isoenzymes) to the sarcolemma, phosphorylation of protein, and a slow contraction. Prolonged association of the kinase with the membrane may lead to proteolysis and release into the cytosol of protein kinase M, resulting in myosin phosphorylation and relaxation.
Hypertension 1992 Nov
PMID:Protein kinase C of smooth muscle. 142 8

Calmodulin is the most important intracellular receptor protein for the second messenger calcium. The calcium-calmodulin complex regulates a number of physiological processes. An increasing number of pharmaceutical products is reported to interfere with the calcium-calmodulin complex. Despite the fact that the precise mechanisms of action of these so-called calmodulin antagonists await further clarification, reports accumulate in the literature indicating a broadening spectrum of putative therapeutic applications of calmodulin antagonists. Some of these applications, such as in cell proliferation, hypertension, congestive heart failure, arrhythmia and gastro-intestinal disorders, are discussed in the present review.
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PMID:Putative therapeutic applications of calmodulin antagonists. 143 93

1. In addition to metabolic and neurohumoral factors endothelium-derived autacoids like the nitric oxide radical NO and prostacyclin are effective regulators of vascular tone and thus tissue perfusion. NO is produced in endothelial cells from L-arginine by a Ca2+/calmodulin-dependent enzyme NO synthase. In addition, the NO radical is ultimately cleaved from all nitrovasodilators and resembles their vasoactive and antiaggregatory principle, which is used under pathological conditions as substitution therapy for impaired endothelial function and autacoid production. Impaired endothelium-dependent vasomotor control has been documented in hypercholesterolaemia, atheromatosis, diabetes, hypertension, and in reperfusion damage. L-arginine supplementation is effective in a few instances.
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PMID:Clinical relevance of endothelium-derived relaxing factor (EDRF). 163 78

Intracellular calcium concentration ([Ca2+]i)-dependent activation of myosin light chain kinase and its phosphorylation of the 20-kd light chain of myosin is generally considered the primary mechanism responsible for regulation of contractile force in arterial smooth muscle. However, recent data suggest that the relation between [Ca2+]i and myosin light chain phosphorylation is variable and depends on the form of stimulation. The dependence of myosin phosphorylation on [Ca2+]i has been termed the "[Ca2+]i sensitivity of phosphorylation." The [Ca2+]i sensitivity of phosphorylation is "high" when relatively small increases in [Ca2+]i induce a large increase in myosin phosphorylation. Conversely, the [Ca2+]i sensitivity of phosphorylation is "low" when relatively large increases in [Ca2+]i are required to induce a small increase in myosin phosphorylation. There are two proposed mechanisms for changes in the [Ca2+]i sensitivity of phosphorylation: Ca(2+)-dependent decreases in the [Ca2+]i sensitivity of phosphorylation induced by phosphorylation of myosin light chain kinase by Ca(2+)-calmodulin protein kinase II and agonist-dependent increases in the [Ca2+]i sensitivity of phosphorylation by inhibition of a myosin light chain phosphatase. I will review the proposed mechanisms responsible for the regulation of [Ca2+]i and the [Ca2+]i sensitivity of phosphorylation in arterial smooth muscle.
Hypertension 1992 Aug
PMID:Regulation of contraction and relaxation in arterial smooth muscle. 163 54

Since Ca2+ ions seem to directly participate in the control of erythrocyte membrane structure and deformability and because cell Ca2+ metabolism has been repeatedly proposed to be modified in hypertension, the intracellular calcium ion concentration ([Ca2+]i) was investigated in red blood cells from hypertensive and normotensive subjects. [Ca2+]i was measured by using the fluorescent Ca2+ chelator fura-2. Red blood cell [Ca2+]i was increased in hypertensive compared with normotensive subjects in the whole population and further increased when hypertensive were compared with age-matched normotensive subjects. An inverse relation between age and [Ca2+]i was observed when calculated with blood pressure adjusted. In hypertensive patients, high [Ca2+]i values were associated with a reduced erythrocyte deformability. The initial rate of 45Ca2+ uptake did not differ between the two blood pressure groups. Similarly, when the extracellular Ca2+ concentration was elevated from 1 to 2 mmol/l, [Ca2+]i increased by 16 +/- 4% (p less than 0.03) in red blood cells from both groups, thus maintaining a significant difference between hypertensive and normotensive subjects. Under these conditions, the addition of 10(-7) mol/l nicardipine, a dihydropyridine Ca2+ antagonist, decreased [Ca2+]i by 15 +/- 4% (p less than 0.05) and 7 +/- 5% in erythrocytes from hypertensive and normotensive subjects, respectively, thereby reducing the difference in [Ca2+]i observed between these two groups. This nicardipine effect was positively correlated to the initial [Ca2+]i. In the presence of 5 mumol/l W7, a calmodulin antagonist, [Ca2+]i increased significantly only in erythrocytes from hypertensive patients (26 +/- 6%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Control of the erythrocyte free Ca2+ concentration in essential hypertension. 173 51

The exaggerated response to growth factors of vascular smooth muscle cells from spontaneously hypertensive rats when compared to cells from normotensive control Wistar-Kyoto rats persists in culture, indicating an intrinsic/genetic defect. The time course of 3H-thymidine incorporation shows that synchronized vascular smooth muscle cells from spontaneously hypertensive rats start to synthesize new DNA earlier after mitogenic stimulation than cells from normotensive rats. Flow cytometry demonstrates that in cell populations growing in 10% calf serum for three d there is a higher proportion of cells from spontaneously hypertensive rats in the S phase of the cell cycle. The same proportions in the G2 + M phase of growing, as well as synchronized cells from normotensive and hypertensive rats indicate no difference in polyploidy. Forward light scatter analysis reveals no difference in cell size. These results suggest that the growth kinetic of vascular smooth muscle cells from normotensive and spontaneously hypertensive rats are different. Since the defect seems to be in the prereplicative phase of the cell cycle susceptible to regulation by extrinsic factors, we studied the effect of the calmodulin inhibitor, W-7, on DNA synthesis. The comparable IC50 of W-7 to inhibit cell growth of vascular smooth muscle cells of both origins indicates that the defect may not be due only to calmodulin, and furthermore suggests the involvement of a previously-reported calmodulin activator in hypertension.
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PMID:Intrinsic factors involved in vascular smooth muscle cell proliferation in hypertension. 179 7

EDRF is a potent, endogenous vasodilator that is produced and released from endothelial cells and subsequently causes the relaxation of VSM through the activation of soluble guanylate cyclase and an increase in VSM cyclic GMP. Structurally, EDRF is likely to be NO or a related nitrogen oxide-containing compound. It is synthesized in endothelial and other cell types from L-arginine by a calcium-calmodulin and NADPH-dependent enzyme. Its action is very similar to the nitrovasodilators that act directly on VSM. EDRF is present in all vascular beds, large and small vessels, and in a wide range of species. Its role in human vascular physiology and pathophysiology is just beginning to be understood. EDRF is a potent endogenous vasodilator and inhibitor of platelet aggregation and adhesion. Its activity is impaired in hypertension and atherosclerosis, and its absence due to endothelial damage may play a role in cerebral and coronary vasospasm. It is a mediator of flow-dependent vasodilation, and its inhibition by hypoxia may contribute to the hypoxic pulmonary vasoconstrictor response. Endothelial cell damage and impairment of EDRF production may also contribute to acute and chronic pulmonary hypertension. A further understanding of the chemical nature and synthetic pathways of EDRF should lead to the production of analogs and antagonists, which may play an important role in future treatments for atherosclerosis, myocardial infarction, angina, hypertension, and other vascular diseases. The recent realization that EDRF serves as the second messenger for guanylate cyclase activation and cyclic GMP production in a variety of cell types outside of the cardiovascular system, including renal and respiratory epithelium, cerebellar neurons, macrophages, and adrenocytes, suggests even broader implications. The importance of EDRF to the anesthesiologist may go beyond an understanding of its role in cardiovascular physiological and pathophysiological states. Initial studies have shown that the endothelium may play a role in mediating the vascular actions of anesthetics, and that anesthetics can inhibit the production, release, or action of EDRF. How are these interactions mediated? Are there significant differences between anesthetics with regard to their effects on EDRF? Is there a clinically significant effect of anesthetics on basal activity of EDRF, or only in response to exogenous stimulation? Conversely, it is important to determine if alterations in endothelial cell function by various disease states such as hypertension, atherosclerosis, adult respiratory distress syndrome, cerebral vasospasm, and others cause changes in the vascular actions of anesthetics. The potential interactions of anesthetics with EDRF production and action in cell types other than the endothelium have not yet been explored.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endothelium-derived relaxing factor: basic review and clinical implications. 186 89

For many years the simple view was held that contractile force in smooth muscle was proportional to cytosolic Ca2+ concentrations ([Ca2+]i). With the discovery that phosphorylation of myosin light chain by Ca2+/calmodulin-dependent myosin light chain kinase initiated contraction, regulation of the contractile elements developed more complex properties. Molecular and biochemical investigations have identified important domains of myosin light chain kinase: light chain binding sites, catalytic core, pseudosubstrate prototope, and calmodulin-binding domain. New protein phosphatase inhibitors such as okadaic acid and calyculin A should help in the identification of the physiologically important phosphatase and potential modes of regulation. The proposal of an attached, dephosphorylated myosin cross bridge (latch bridge) that can maintain force has evoked considerable controversy about the detailed functions of the myosin phosphorylation system. The latch bridge has been defined by a model based on physiological properties but has not been identified biochemically. Thin-filament proteins have been proposed as secondary sites of regulation of contractile elements, but additional studies are needed to establish physiological roles. Changes in the Ca2+ sensitivity of smooth muscle contractile elements with different modes of cellular stimulation may be related to inactivation of myosin light chain kinase or activation of protein phosphatase activities. Thus, contractile elements in smooth muscle cells are not dependent solely on [Ca2+]i but use additional regulatory mechanisms. The immediate challenge is to define their relative importance and to describe molecular-biochemical properties that provide insights into proposed physiological functions.
Hypertension 1991 Jun
PMID:Vascular smooth muscle contractile elements. Cellular regulation. 204 32


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