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

1. The effects on blood pressure and on pressor responses to noradrenaline (NA), of NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME), inhibitors of the L-arginine/nitric oxide pathway, were investigated in anaesthetized rats receiving an infusion of bacterial endotoxin (E. coli lipopolysaccharide, LPS). 2. Infusion of LPS (10 mg kg-1 h-1) for 50 min had no effect on mean arterial blood pressure (MABP) but induced a reduction in responsiveness to noradrenaline (100 ng-1 micrograms kg-1). L-NMMA (30 mg kg-1), but not D-NMMA, caused an increase in MABP of approximately 30 mmHg and restored responses to NA. This effect was reversed by L- but not D-arginine (100 mg kg-1). 3. In LPS-treated rats, blood pressure responses to NA were only marginally increased by the cyclooxygenase inhibitor, indomethacin (5 mg kg-1). L-NAME (1 mg kg-1) caused a similar increase in MABP and restored pressor responses to NA both in the presence and absence of indomethacin. 4. Co-infusion of vasopressin (100 ng kg-1, for 10 min) with LPS (10 mg kg-1 h-1) in order to reproduce the hypertensive effect of L-NMMA and L-NAME increased pressor responsiveness to 100 and 300 ng kg-1 NA but not to 1 microgram kg-1 NA. 5. Infusion of sodium nitroprusside (30 micrograms kg-1 min-1) decreased responsiveness to NA even when the hypotension was corrected by co-infusion of vasopressin (50 ng kg-1 min-1). 6. These results demonstrate that the restoration of vascular responsiveness to NA in LPS-treated anaesthetized rats by inhibitors of the L-arginine/nitric oxide pathway is stereospecific and reversible. Furthermore, the experiments involving indomethacin suggest that although cyclo-oxygenase products of arachidonic acid may contribute to the development of LPS-induced hyporeactivity, the effect of L-NAME is unlikely to involve inhibition of the cyclo-oxygenase pathway. Comparison of NA responsiveness during vasopressin and L-NMMA/L-NAME-induced hypertension shows that increasing the blood pressure may modify LPS-induced hyporeactivity, but cannot account for the complete restoration of responses to NA by L-NMMA and L-NAME. These observations suggest that activation of nitric oxide formation from L-arginine makes a direct contribution to the production of vascular hyporeactivity by LPS in vivo.
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PMID:The effect of inhibitors of the L-arginine/nitric oxide pathway on endotoxin-induced loss of vascular responsiveness in anaesthetized rats. 190 34

The effect of nitric oxide (NO) pathway inhibitor, NG-monomethyl-L- arginine (L-NMMA), on arterial blood pressure was examined in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs) to investigate whether the vasodilating effect of basal levels of NO, one of the endothelium-derived relaxing factors, is preserved during the development of hypertension. L-NMMA (1-100 mg/kg i.v.) produced dose-dependent increase in arterial pressure and bradycardia in anesthetized and conscious SHRs and WKYs. L-Arginine, a precursor of NO, inhibited the pressor response to L-NMMA. The L-NMMA-induced increases in arterial pressure in both 5- to 6- and 12- to 13-week (wk)-old anesthetized SHRs were similar to those of age-matched WKY controls; rather, the increase was significantly larger in 53- to 54-wk-old SHRs than in the age-matched WKYs. In conscious SHRs (13-14 wk-old), L-NMMA induced larger hypertensive effect than in the age-matched WKYs. The amplitude of acetylcholine (ACh)-induced hypotension was somewhat larger in 5- to 6- and 12- to 13-wk-old anesthetized SHRs compared with the age-matched WKY controls. The duration of the hypotension in 5- to 6- and 12- to 13-wk-old anesthetized SHRs was similar to the age-matched WKY controls. L-NMMA significantly reduced the duration of the ACh-induced hypotension; an effect which was recovered by L-arginine. However, L-NMMA did not decrease the amplitude of the hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:NG-monomethyl-L-arginine-induced pressor response at developmental and established stages in spontaneously hypertensive rats. 192 Jan 34

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

As a source of several vasoactive factors, the endothelium takes part in the regulation of vascular tone. The most important endothelium-derived vasoactive substances are nitric oxide, prostacyclin, endothelin-1 and contracting factors requiring the activity of cyclooxygenase. The endothelium is an obvious target organ of cardiovascular risk factors. Accordingly, functional alterations do occur with aging, hypertension, and lipids. All three conditions are associated with a decreased basal and stimulated release of endothelium-derived nitric oxide. On the other hand, the release of endothelin-1 appears to increase with age, while the sensitivity to the peptide markedly decreases under the same conditions. In the spontaneously hypertensive rat, acetylcholine and stretch evoke the release of cyclooxygenase-dependent endothelium-derived contracting factor, most likely prostaglandin H2. The sensitivity and circulating levels of endothelin-1, on the other hand, are reduced in this experimental model of hypertension. In the porcine coronary circulation, oxidized low-density lipoproteins selectively reduce endothelium-dependent relaxations to aggregating platelets, serotonin, and thrombin which are mediated by nitric oxide. The alterations of endothelial function occurring with aging, hypertension, and hyperlipidemia may have important clinical implications for the pathogenesis of cardiovascular disease.
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PMID:Endothelium-dependent control of vascular tone: effects of age, hypertension and lipids. 195 6

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

In addition to the classical transmitters noradrenaline and acetylcholine, other transmitters have been identified in perivascular nerves, including 5-hydroxytryptamine, ATP and a number of peptides. This paper discusses pre- and postjunctional neuromodulation of vascular transmission, and cotransmission involving noradrenaline, ATP and neuropeptide Y in sympathetic nerves, acetylcholine and vasoactive intestinal polypeptide in parasympathetic nerves, and substance P, calcitonin gene-related peptide and ATP in 'sensory-motor' nerves. Vasomotor nerves derived from intrinsic neurones, for example in the heart and gut, are also discussed. Subpopulations of endothelial cells store and release a variety of substances, including acetylcholine, substance P, ATP, 5-hydroxytryptamine, vasopressin and angiotensin II, that act on receptors on endothelial cells and lead to the production of endothelium-derived relaxing factor (identified as nitric oxide) which, in turn, produces vasodilation in response to changes in flow and hypoxia. Endothelium-derived contracting factors such as endothelin may also be released. There appears to be a resting dynamic balance between endothelium-derived vasodilator tone and sympathetic vasoconstrictor tone, which is altered under different physiological and pathophysiological circumstances. Long-term (trophic) interactions between perivascular nerves and endothelial cells are discussed, as are the changes in vascular control mechanisms that occur with ageing and hypertension and in the nerves that remain following trauma or surgery.
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PMID:Local mechanisms of blood flow control by perivascular nerves and endothelium. 198 71

An in vitro bioassay system was developed to study endothelium-mediated, shear stress-induced, or flow-dependent generation of endothelium-derived relaxing factor (EDRF). Monolayers of aortic endothelial cells were grown on a rigid and large surface area of microcarrier beads and were packed in a small column perfused with Krebs bicarbonate solution. The perfusate was allowed to superfuse three endothelium-denuded target pulmonary arterial strips arranged in a cascade. Fluid shear stress caused a flow-dependent release of EDRF from the endothelial cells. The action of EDRF was abolished by oxyhemoglobin and methylene blue, and the generation of EDRF in response to shear stress was markedly inhibited or abolished by NG-nitro-L-arginine, by NG-amino-L-arginine, by calcium-free extracellular medium, and by depleting endothelial cells of endogenous L-arginine. Addition of L-arginine to arginine-deficient but not arginine-containing endothelial cells rapidly restored the capacity of shear stress and bradykinin to generate EDRF. These observations indicate that fluid shear stress causes the generation of EDRF with properties of nitric oxide from aortic endothelial cells and that the bioassay system described may be useful for studying the mechanism of mechanochemical coupling that leads to nitric oxide generation.
Hypertension 1991 Feb
PMID:Shear stress-induced release of nitric oxide from endothelial cells grown on beads. 199 51

The functions of the endothelium and the effects of hypertension, atherosclerosis, and diabetes on the endothelium are reviewed. The endothelium affects vascular tone by releasing vasodilators and modulating the effects of vasoactive substances such as catecholamines, bradykinin, serotonin, and angiotensin II. Relaxation of vascular smooth muscle depends upon a functionally intact endothelium and the release of the endothelium-derived relaxing factor nitric oxide. Endothelial cells also appear to release a hyperpolarizing factor that relaxes smooth muscle through activation of the sodium-potassium pump, and of the endothelium-dependent contracting factors. Similarities are found in the vascular injury resulting from hypertension, atherosclerosis, and diabetes. When these risk factors coexist, they can act synergistically and magnify the vascular injury. The endothelium appears to be one of the major targets for these forms of injury. Future therapeutic strategies will focus on ways to prevent, arrest, or reverse endothelial injury.
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PMID:Hypertension, endothelium, and cardiovascular risk factors. 199 9

Nitric oxide (NO) has been identified as a naturally-occurring metabolite in mammalian systems, formed from the amino acid arginine in response to a variety of physiological stimuli. It appears to function in cell-cell communication and may act either directly or through the stimulation of cyclic GMP synthesis in the regulation of such diverse functions as smooth muscle relaxation, inhibition of platelet aggregation and adhesion, central nervous system activity, and cytostasis. The significant role(s) could have important biomedical implications since perturbations in the biosynthesis, release or actions of NO could lead to hypertension, CNS dysfunction or increased susceptibility to infection. Understanding the enzymology and regulation of this pathway in various tissues may lead to development of pharmacological agents specifically designed for the rational control of nitric oxide formation and action.
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PMID:Nitric oxide. New discoveries, biomedical implications. 202 96

Ingestion of protein or intravenous infusion of amino acids acutely elevates glomerular filtration rate (GFR) and renal plasma flow (RPF) by unknown mechanisms. Endothelium-derived relaxing factor (EDRF), now known to be nitric oxide derived from metabolism of L-arginine, participates in local regulation of vascular tone. To investigate the hypothesis that EDRF may participate in the renal vasodilatation and increased GFR after amino acid infusion, we characterized the effect of inhibition of EDRF synthesis with NG-monomethyl L-arginine (LNMMA) on basal renal hemodynamics and the response to infusion of a 10% mixed amino acid solution (1 ml/hr i.v.) in the rat. Renal arterial infusion of LNMMA (500 micrograms/kg/min) resulted in a significant increase in mean arterial pressure, decreases in GFR (20%) and RPF (44%), and a significant increase in filtration fraction. Pretreatment with the angiotensin II receptor antagonist Sar-Gly-angiotensin II did not prevent the increase in blood pressure but blunted the decreases in GFR (11%) and RPF (27%) after LNMMA infusion. Amino acid infusion in the untreated, fasted rat resulted in no change in blood pressure but significant increases in GFR and RPF; these effects were completely inhibited by intrarenal LNMMA but not an equihypertensive intravenous infusion of phenylephrine. In summary, EDRF participates in regulation of basal renal hemodynamics. Furthermore, amino acid-induced hyperfiltration and renal vasodilatation are completely prevented by inhibition of EDRF synthesis. We conclude that EDRF may participate in the renal hemodynamic response to amino acid infusion.
Hypertension 1991 Jun
PMID:Effects of amino acid infusion on renal hemodynamics. Role of endothelium-derived relaxing factor. 204 48


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