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

Evidence continues to accumulate on the importance of paracrine substances formed in the vascular endothelium in the regulation of the vascular system. Those that relax the underlying smooth muscle include nitric oxide, prostacyclin, and an unidentified hyperpolarizing factor; those causing contraction include angiotensin II, endothelin, oxygen-derived free radicals, prostacyclin H2, and thromboxane A2. Determination of the mechanisms governing the formation and release of these substances in different blood vessels of the same species and in different species as well as the maintenance of the balance between them is important for understanding their role in normal circumstances and in diseases of the blood vessels. In this article, we will summarize the current understanding of the role of endothelium-derived relaxing factors and discuss the possibility that endothelial dysfunction may play a primary as well as a secondary role in the pathogenesis of primary hypertension. As a consequence of this dysfunction, substances formed in the endothelial cells at the sites of the arterial baroreceptors could lead to their resetting, resulting in less inhibition of the vasomotor centers, enhanced neurohumoral activity, and a consequential increase in systemic vascular resistance. This increase could be enhanced by a predominant action of endothelium-derived contracting factors in the resistance vessels. Proliferation of the vascular smooth muscle would follow, because of the mitogenic action of some of these factors and other growth promotors. By these mechanisms, the endothelium may participate in the polygenic dysfunction characteristic of primary hypertension, not only in initiating the increase in arterial blood pressure, but also in sustaining it.
Hypertension 1991 Nov
PMID:Endothelium-derived vasoactive factors: I. Endothelium-dependent relaxation. 193 90

The immunosuppressive drug cyclosporin A (CsA) frequently induces hypertension, but the mechanism(s) is unknown. Thus, we examined the mechanism(s) by which CsA increases arterial blood pressure (MAP) in the normotensive rat. Three different treatment modalities were used. First, chronic CsA treatment (20 mg/kg/day, s.c., for 1 week) significantly increased MAP from 109.6 +/- 2.3 mm Hg to 125.8 +/- 2.9 mm Hg (P less than .05). Second, subacute i.v. infusion of CsA (20 mg/kg daily for 3 days) increased MAP to even higher values (140.5 +/- 2.3 mm Hg), which correlated significantly with the highest circulating values of the drug. The pressor effect after i.v. infusion appears to be unrelated to endogenous release of catecholamines, because phentolamine, which abolishes the response to exogenous norepinephrine, failed to prevent the CsA-induced pressor response. Third, i.v. bolus injections of CsA (10-20 mg/kg) evoked immediate, dose-dependent and short-lasting increases in MAP (+15-25 mm Hg) in both anesthetized and conscious rats. Ganglionic blockade did not prevent this effect, rather, a 2- to 3-fold increase in amplitude (+40-60 mm Hg) and duration (+30-45 min) of the CsA-induced pressor response was observed in anesthetized rats. Heart rate was not increased significantly by either acute or chronic administration of CsA. Our results suggest that both CsA-induced pressor responses and hypertension are due to a peripheral action unrelated to sympathetic outflow. Furthermore, CsA's hypertensive effect is accompanied by severe morphological changes in the vascular endothelium and smooth muscle cells. In addition, CsA-treated rats showed significantly attenuated vasodilatory responses to prostacyclin and sodium nitroprusside, and increased pressor responses to norepinephrine. Thus, a direct vascular action of CsA is likely to contribute to the alterations on systemic vascular responsiveness, as well as to the hypertensive effect of the drug.
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PMID:Systemic vascular effects of cyclosporin A treatment in normotensive rats. 194 35

Nitric oxide first captured the interest of biologists when this inorganic molecule was found to activate cytosolic guanylate cyclase and stimulate cyclic guanosine monophosphate (GMP) formation in mammalian cells. Further studies led to the finding that nitric oxide causes vascular smooth muscle relaxation and inhibition of platelet aggregation by mechanisms involving cyclic GMP and that several clinically used nitrovasodilators owe their biological actions to nitric oxide. Nitric oxide possesses physicochemical and pharmacological properties that make it an ideal candidate for a short-term regulator or modulator of vascular smooth muscle tone and platelet function. Nitric oxide is synthesized by various mammalian tissues including vascular endothelium, macrophages, neutrophils, hepatic Kupffer cells, adrenal tissue, cerebellum, and other tissues. Nitric oxide is synthesized from endogenous L-arginine by a nitric oxide synthase system that possesses different cofactor requirements in different cell types. The nitric oxide formed diffuses out of its cells of origin and into nearby target cells, where it binds to the heme group of cytosolic guanylate cyclase and thereby causes enzyme activation. This interaction represents a novel and widespread signal transduction mechanism that links extracellular stimuli to the biosynthesis of cyclic GMP in nearby target cells. The small molecular size and lipophilic nature of nitric oxide enable communication with nearby cells containing cytosolic guanylate cyclase. The extent of transcellular communication is limited by the short half-life of nitric oxide, thereby ensuring a localized response. Labile nitric oxide-generating molecules such as S-nitrosothiols may be involved as precursors or effectors. Further research will provide a deeper understanding of the biology of nitric oxide and the nature of associated pathophysiological states.
Hypertension 1990 Nov
PMID:Nitric oxide. A novel signal transduction mechanism for transcellular communication. 197 98

Physiological studies have clarified the role that the brain has in the interplay between salt balance and hypertension. Neural mechanisms and endocrine secretions play a pivotal role in the adaptation of mammals to changes in the intake and excretion of sodium. Maneuvers that alter the concentration of sodium in the plasma modify the sensitivity of baroreceptor reflexes and alter vascular reactivity. These changes may be mediated in part by the release of vasopressin. The research also suggests that the brain indirectly modulates the ability of the vascular endothelium to release vasoactive factors. Collectively, these studies illustrate the multiple effects of the sodium ion on the peripheral neural and central endocrine mechanisms that participate in the regulation of arterial pressure.
Hypertension 1991 Jan
PMID:Neurovascular mechanisms and sodium balance in the pathogenesis of hypertension. 198 11

In addition to preserving the permselectivity of the vascular wall and providing an antithrombogenic surface, the vascular endothelium contributes importantly to the regulation of vasomotor tone. Indeed, the endothelium participates in the conversion of angiotensin I to angiotensin II; the enzymatic inactivation of several plasma constituents such as bradykinin, norepinephrine, serotonin, and ADP; and the synthesis and release of vasodilator substances such as prostacyclin and the recently discovered endothelium-derived relaxing factor (EDRF). The diffusible EDRF released from the endothelium is nitric oxide or a substance closely related to it such as nitrosothiol. The endothelium also synthesizes and releases vasoconstrictive factors, including products derived from arachidonic acid metabolism and the recently discovered peptide endothelin. An increasing body of evidence from experimental and clinical studies indicates that EDRF and endothelium-derived contracting factors play an important role in vascular physiology and pathology. It has become apparent that the balance of these factors may be a major determinant of systemic and regional hemodynamics. Moreover, through generally opposite effects on growth-related vascular changes, contracting factors such as endothelin and relaxing factors such as EDRF also may be important determinants of the vascular response to injury in various disease states such as atherosclerosis and hypertension. It is clear that the vascular endothelium is a complex and dynamic organ. Understanding endothelium function in normal physiology and disease states is of potential clinical importance and should be the focus of future investigation.
Hypertension 1991 Jun
PMID:Role of endothelium-derived relaxing factor in regulation of vascular tone and remodeling. Update on humoral regulation of vascular tone. 204 72

The intravascular distribution of 0.2 mu lipid microspheres (LM) containing prostaglandin E1 (lipo-PGE1) injected intravenously in spontaneously hypertensive rats (SHR) and arteriosclerotic rabbits was investigated by electron microscopic observation and quantification of radiolabelled compounds. LM were observed under an electron microscope to concentrate in subendothelial space of vascular walls, particularly in vascular lesions associated with hypertension or arteriosclerosis. Radiolabelled lipo-PGE1 accumulated more densely in the vascular walls than did free PGE1, and the difference was more conspicuous in vascular lesions. This indicates that lipo-PGE1 penetrates vascular endothelium and then accumulates in blood vessels to result in augmentation of the pharmacological action of prostaglandin. These findings suggest the usefulness of LM as a carrier of prostaglandin to vascular lesions.
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PMID:Distribution of lipid microspheres incorporating prostaglandin E1 to vascular lesions. 207 41

Prostacyclin and endothelium-derived relaxing factor (or nitric oxide) are unstable mediators produced by the vascular endothelium, that are important for local regulation of platelet behavior and blood flow. This review focuses on the basic biochemistry and pharmacology of prostacyclin, its interactions with nitric oxide and nitrovasodilator drugs, and the implications of disturbances in this system for vascular disease, particularly hypertension and atherosclerosis. Prostacyclin and its stable analogs are also finding limited therapeutic applications in preservation of platelet function, pulmonary hypertension, and investigation into the cytoprotective and antiatherosclerotic properties is continuing.
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PMID:Prostacyclin and vascular function: implications for hypertension and atherosclerosis. 208 4

This paper review the actual knowledges about the physiological role of nitric oxide, sintetized from amino acid L-arginine. The nitric oxide sintetized in the vascular endothelium has a fundamental role in vascular tone, blood flow and arterial pressure control, acting stimulating guanylate cyclase on vascular smooth muscle. Nitric oxide could be considered the endogenous nitrovasodilator. Its action on the cardiovascular system are imitated by nitroglycerine, sodium nitroprusside and related compounds. Probably the disturbance in the synthesis or release of nitric oxide may be involved in the pathophysiology of hypertension, vasospasm and atherosclerosis. Recently has been shown that nitric oxide synthesis from L-arginine also occurs in other different cells like macrophages, central nervous system, liver, neutrophils, adrenal glands, playing different biological effects. Changes in nitric oxide synthesis or action in those systems, could be related to different pathological disorders as inflammation, atherosclerosis and cancer. The found of a substance as simple as nitric oxide, let suppose that we are in the presence of a biological mediator with a very early evolutionary origin, probably widespread in all the animal kingdom, and which represents the universal transduction system for activation of the soluble guanylate cyclase enzyme.
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PMID:[Nitric oxide: from endogenous vasodilator to biologic mediator]. 209 54

The aim of this study was to verify the possible role of serotonin on vascular basal tone and over-reactivity in systemic and pulmonary circuits in hypertensive patients. We studied 15 hypertensive (G1) and 10 normotensive (G2) subjects. Right-side pressure and intravascular-arterial pressure measurements were obtained in baseline conditions and during alpha-adrenergic activation by cold-pressor-test (CPT), before and after intravenous injection of ketanserin 10 mg (K), an S2-receptor antagonist. Systemic and pulmonary pressures and resistances were higher in G1 than in G2 in the steady state. K induced a significant reduction of both pressures and resistances in G1, no change in systemic response to CPT in the 2 groups and a significant reduction in the pulmonary vascular reactivity to adrenergic stimulus only in G1. These data confirm the vasodilator action of serotonin-blockade. The observation of vasodilatation in pulmonary circulation is not in favor of its dependence on vascular endothelium damage. In fact the arterial endothelium lesions due to hypertension are present only in the systemic circuit. Concerning result of CPT: 1) serotonin doesn't seem responsible for vascular over-reactivity in hypertension, unchanged by K; 2) the particular pattern of pulmonary vascular contractility in G1 may be interpreted as resulting from an elective depressive action of S2-blockade, depending on a different distribution of S1 and S2 receptors in the two circuits.
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PMID:[Effects of serotoninergic block on reactivity of systemic and pulmonary circulation in hypertensive patients]. 210 31

In open-chest anesthetized dogs acute hypertension causes neutrophil and platelet adhesion to vascular endothelium and selectively potentiates constriction to serotonin in proximal coronary arteries. To examine underlying mechanisms, canine left anterior descending coronary arteries subjected to 15 min hypertension (LAD-HYP) and control left circumflex coronary arteries (CX) perfused at normal pressure were studied in organ chambers. In endothelium-intact LAD-HYP rings, constriction to serotonin was potentiated fourfold compared with control CX rings but was similar in denuded LAD-HYP and CX vessels. Endothelium-dependent relaxation to acetylcholine was not affected by acute hypertension. In LAD-HYP rings 10 microM LY 83583 (which depletes guanosine 3',5'-cyclic monophosphate and inhibits effects of endothelium-derived relaxing factor) augmented constriction to serotonin twofold. LY 83583 did not affect the serotonin response in hypertensive rings whose endothelium was mechanically removed. Blockade of either leukotriene D4 (LTD4) receptors (either with LY 171883 or SKF 102992) or thromboxane A2 (TxA2) receptors (with SQ 29548) partially blunted constriction to serotonin. Combined LTD4- and TxA2-receptor blockade completely normalized serotonin-induced constriction in LAD-HYP rings. In preconstricted LAD-HYP rings, relaxations to serotonin were markedly impaired but were restored by addition of ketanserin. Normalization of relaxation to serotonin in hypertensive vessels by ketanserin is likely due to inhibition of 5-hydroxytryptamine2 (5-HT2) receptors on platelet membranes. In conclusion, augmented constriction to serotonin in canine epicardial vessels exposed to acute hypertension is not due to an impairment of endothelium-dependent relaxation to the amine but to concomitant release of leukotrienes and TxA2 from leukocytes and platelets adhering to damaged endothelium. Activation of 5-HT2 serotonergic receptors on platelet membranes could be a possible trigger mechanism.
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PMID:Leukocyte and platelet-derived factors augment canine coronary constriction to serotonin. 217 64


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