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

1. Endothelial cells of blood vessels generate factors which can modulate underlying smooth muscle tone, inducing vasorelaxation, (endothelium-derived relaxing factor, EDRF, and endothelium-derived hyperpolarizing factor) and/or vasoconstriction (endothelium-derived contracting factors, EDCFs, including the peptide endothelin). 2. EDRF is nitric oxide (NO) or a RNO compound from which this oxide is released. Its half-life is very short (6-50 sec), and it produces rapid vasodilations and inhibits platelet aggregation. 3. NO is formed from the terminal guanidino of L-arginine, but not of D-arginine. NO effects and NO formation are inhibited by NG-monomethyl-L-arginine (L-NMMA), but not by D-NMMA. These inhibitory effects are blocked by L-arginine. 4. Removal of endothelium or pathological situations that can induce endothelial dysfunction (atherosclerosis, diabetes, hypertension or subarachnoid hemorrhage) cause increases on the vascular contractility elicited by agonists (noradrenaline, serotonin, EDCFs, etc.). These findings suggest that EDRF produces a physiological inhibitory modulation of vascular smooth muscle tone and its alteration produces or facilitates the development of diseases such as hypertension or coronary and cerebral vasospasm.
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PMID:Role of endothelium-formed nitric oxide on vascular responses. 227 79

Homozygous Brattleboro (i.e. vasopressin-deficient) rats were chronically instrumented with pulsed Doppler probes and intravascular catheters to permit continuous monitoring of regional haemodynamics. Over a 9 h period, rats drinking water showed no systematic changes in heart rate or mean arterial blood pressure although renal, mesenteric and hindquarters vascular conductances fell. These changes showed diurnal rhythms, probably related to the nocturnal habits of rats. In separate groups of animals spontaneous oral ingestion of NG-monomethyl-L-arginine (L-NMMA; 1 mg ml-1) or NG-nitro-L-arginine methyl ester (L-NAME; 0.1 mg ml-1) caused marked hypertension but no significant bradycardia. Compared to control animals, rats drinking L-NMMA for 9 h showed significantly greater mesenteric and hindquarters vasoconstrictions, and rats drinking L-NAME showed greater vasoconstrictions in all 3 vascular beds.
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PMID:Regional haemodynamic changes during oral ingestion of NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester in conscious Brattleboro rats. 228 51

The regional hemodynamic consequences of inhibiting vascular endothelial nitric oxide generation with NG-monomethyl-L-arginine (L-NMMA) were studied in conscious Long-Evans rats. Experiments were carried out in groups of chronically instrumented rats with intravascular catheters and pulsed Doppler probes to monitor regional blood flow. L-NMMA (0.3-300 mg/kg) caused a dose-dependent, long-lasting (5-90 minutes), and enantiomerically specific increase in mean blood pressure and also caused bradycardia. The increase in blood pressure was accompanied by a dose-dependent and long-lasting vasoconstriction in the internal carotid, mesenteric, renal, and hindquarters vascular beds that could be attenuated, in a concentration-dependent manner, by L-arginine but not by D-arginine. In contrast, L-arginine did not affect the pressor or vasoconstrictor effects of vasopressin. These results indicate that nitric oxide production by vascular endothelial cells contributes to the maintenance of blood pressure and to the control of the resting tone of different vascular beds in the conscious rat.
Hypertension 1990 May
PMID:Control of regional blood flow by endothelium-derived nitric oxide. 233 39

Intrarenal infusion of acetylcholine in meclofenamate-treated dogs significantly increased renal blood flow, diuresis, and natriuresis. Intrarenal infusions of either NG-monomethyl-L-arginine (inhibitor of endothelium-derived relaxing factor formation), or L-arginine (precursor of endothelium-derived relaxing factor formation) did not modify basal levels of those parameters. However, the infusion of NG-monomethyl-L-arginine inhibited the acetylcholine-induced increases in renal blood flow and diuresis without affecting natriuresis, which increased significantly. The infusion of L-arginine failed to further enhance hemodynamic and excretory effects elicited by acetylcholine. The concomitant infusion of L-arginine and NG-monomethyl-L-arginine did not change renal blood flow, urine flow, or sodium excretion rate. L-Arginine administration prevented the inhibitory effect of NG-monomethyl-L-arginine on acetylcholine-induced renal vasodilatation and diuresis. Glomerular filtration rate and mean arterial pressure did not change throughout the experiment. The results indicate that the vasodilatory and diuretic responses to intrarenal acetylcholine in meclofenamate-treated dogs are largely dependent on endothelium-derived relaxing factor.
Hypertension 1990 Jun
PMID:Effects of NG-monomethyl-L-arginine and L-arginine on acetylcholine renal response. 234 26

In conduit arteries, nitric oxide is formed from L-arginine in the endothelium and released after stimulation with acetylcholine. The contribution of the L-arginine pathway and the effects of age and hypertension on endothelium-dependent vascular regulation were studied, using a video dimension analyzer, in pressurized and perfused mesenteric resistance arteries of 8- and 16-20-week-old Wistar-Kyoto and spontaneously hypertensive rats. Norepinephrine and phenylephrine caused contractions, which were similarly augmented after removal of the endothelium. NG-Monomethyl-L-arginine, an inhibitor of nitric oxide formation, augmented the contraction, but less than endothelial removal. Acetylcholine caused endothelium-dependent relaxations that were much more pronounced with intraluminal than with extraluminal application. NG-Monomethyl-L-arginine, methylene blue, and hemoglobin only partially inhibited the response. With aging, the endothelium-dependent inhibition of the response to norepinephrine decreased in Wistar-Kyoto rats; in spontaneously hypertensive rats this inhibition was smaller as compared with age-matched Wistar-Kyoto rats. In Wistar-Kyoto rats, the difference between intraluminal and extraluminal activation became more pronounced in adult rats. In the adult but not the young spontaneously hypertensive rats, the response to intraluminal but not extraluminal acetylcholine was reduced as compared with Wistar-Kyoto rats. Thus, in mesenteric resistance arteries of the rat, nitric oxide is released from L-arginine under basal conditions and after stimulation with acetylcholine but only in part accounts for endothelium-dependent responses. With aging and hypertension, the inhibitory effects of the endothelium against norepinephrine-induced contractions decrease. In hypertension, the intraluminal but not extraluminal activation of the release of endothelium-derived relaxing factors is impaired.
Hypertension 1990 Aug
PMID:Activation of endothelial L-arginine pathway in resistance arteries. Effect of age and hypertension. 237 50

The endothelium modulates coronary vascular tone by the release of endothelium-derived relaxing or contracting substances. The endothelium-derived relaxing factor has been identified as nitric oxide synthesized in endothelial cells from L-arginine. The endothelium can release other relaxing substances such as prostacyclin and a hyperpolarizing factor. Endothelin-1 is a potent vasoconstrictor peptide formed by endothelial cells, and is likely to be the physiologic antagonist of endothelium-derived relaxing factor. Other putative contracting factors include superoxide anions and products of arachidonic acid metabolism. Endothelium-derived relaxing factor is released spontaneously and in response to flow, platelet-derived products (that is, serotonin, thrombin and adenosine diphosphate) and certain autacoids (that is, acetylcholine, bradykinin, histamine, substance P, vasopressin, alpha-adrenergic agonists). A considerable heterogeneity of responses exists among vessels of different size from different anatomic origin and different species. Hypercholesterolemia, atherosclerosis, hypertension and myocardial ischemia or reperfusion, or both, impair endothelium-dependent relaxation. Under normal conditions, endothelium-derived relaxing factor appears to dominate the control of vascular tone of large and small coronary vessels, whereas in disease states, endothelium-derived contracting factors are released. Impairments of endothelial function may be important in the development of various forms of cardiovascular disease.
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PMID:Endothelial control of vascular tone in large and small coronary arteries. 240 18

Rapid inhibition of urokinase in plasma obtained from women in the third trimester of pregnancy was assessed by the addition of 75 IU urokinase per ml plasma, and measurement of residual urokinase activity with PyroGlu-Gly-Arg-pNA after 5 minutes incubation at 37 degrees C. The urokinase inhibitory capacity was markedly increased for the pregnant women compared to non-pregnant controls. Alpha 1-antitrypsin, alpha 2-macroglobulin and alpha 2-antiplasmin did not account for the activity. Inhibition was higher for women with multiple gestations or macrosomia (n = 11) compared to normal pregnant women (n = 35) suggesting that the placenta contributes significantly to the measured activity. Inhibition was lower for women with hypertension (n = 33) compared to the normal pregnant women. Although the etiology for this difference is unclear, the decreased inhibitory activity may contribute to the increased risk for placental abruption that is observed for this group of women.
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PMID:The rapid inhibition of urokinase by plasma from pregnant women at risk for abruptio placenta. 243 78

The endothelium can profoundly affect vascular tone by releasing endothelium-derived relaxing and contracting factor. Nitric oxide (EDRF) is the most important relaxing factor that is released from L-arginine and evokes relaxation by increasing intracellular cyclic GMP in vascular smooth muscle. Endothelin and other endothelium-derived contracting factors (i.e., a cyclooxygenase product and a substance released during hypoxia) may be released as well. In hypertension and atherosclerosis, endothelium-dependent relaxations are impaired and endothelium-dependent contractions may occur, at least in some blood vessels. These changes in endothelium function may promote vasospasm and vascular occlusion and contribute to increased vascular resistance in hypertension. The more effective release of EDRF in arterial coronary bypass grafts-which have a better patency than venous grafts-is in line with the concept that EDRF may play a role in the prevention of vascular occlusion.
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PMID:Endothelium-derived vasoactive substances: potential role in hypertension, atherosclerosis, and vascular occlusion. 247 27

There are four humoral substances which are synthesized in the vascular endothelium: Endothelium Derived Relaxing Factor (EDRF); Endothelium Derived Hyperpolarizing Factor (EDHF); Endothelium Derived Contracting Factor (EDCF) and Prostacyclin. EDRF is identical with nitric oxide (NO), and, under physiological conditions is synthesized in the body from l-arginine. I the release of EDHF muscarinic M1 and M2 receptors are involved (implicated). EDCF (endothelin) is a 21 amino acid peptide (or series of peptides). The authors discuss the role and importance of the endothelum derived factors in different processes under physiological and pathophysiological conditions such as: regulation of the vascular tone, inflammation, trauma, hypertension, arteriosclerosis and aggregation.
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PMID:[The role of blood vessel endothelium in vascular smooth muscle reactivity to biologically active substances and drugs]. 249 Sep 97

Two of the many mediators synthesized by vascular endothelial cells (EC), are involved in maintaining the surface of the normal, healthy endothelium in a non-thrombogenic state. The first is prostacyclin, a product of arachidonic acid metabolism, discovered in 1976. This labile prostanoid, with a half life of approximately 3 minutes, relaxes vascular smooth muscle and inhibits the aggregation of blood platelets. Prostacyclin and its analogues are currently being tested in the clinic for cardiovascular diseases such as primary pulmonary hypertension. A number of drugs including defibrotide, nafazatrom, ronicol and cicletanine may exert their therapeutic effects by releasing prostacyclin from the EC. The second mediator discussed is endothelium-derived relaxing factor (EDRF), discovered in 1980, which also relaxes smooth muscle and inhibits the aggregation and adhesion of platelets. Substances which stimulate release of EDRF include acetylcholine, bradykinin and ADP. EDRF is even more labile than prostacyclin with a half life counted in seconds. It has recently been identified as nitric oxide formed from L-arginine by an unknown mechanism. Prostacyclin and EDRF are released together following stimulation of endothelial receptors and synergize to inhibit platelet aggregation. It is suggested that these mediators form the endothelial defence mechanism against blood-borne cells and chemicals and that breakdown of this barrier results in diseases such as hypertension and atherosclerosis. The peptide, endothelin is the third mediator under discussion. Characterised and synthesised in 1988, it is the most potent vasoconstrictor so far discovered. Three isomers of endothelin have been identified. Paradoxically, endothelin strongly releases both prostacyclin and EDRF thus modulating its own vasoconstrictor actions.
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PMID:Vasoactive mediators derived from the endothelium. 251 50


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