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

Old concepts of an "inert" vascular endothelium have been entirely discredited. It is now known that the vascular endothelium and media form a "functional unit", communicating via both electric and humoral signals. Normal endothelium maintains vascular dilation through release of various dilatory substances, the main one being endothelial relaxing factor (EDRF), which is nitric oxide (NO). EDRF is, for example, released in response to increased shear stress that accompanies high flow rates, and acts by engaging the cyclic GMP system of smooth muscle cells. Even potential vasoconstrictors such as vasopressin, catecholamines and serotonin release EDRF. Endothelial release of prostacyclin supplements the EDRF action. EDRF (and prostacyclin) also inhibit platelet aggregation. In the presence of hypertension and/or atherosclerosis, endothelial function is often impaired and pressor/thrombogenic factors such as endothelin, thromboxane, vasopressin, catecholamines, and serotonin become more dominant. Antihypertensive therapy should, ideally, seek to restore endothelial function to normal.
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PMID:Hypertension and endothelial function--aspects of atheroma protection. 134 64

Nitric oxide (NO), synthesised from L-arginine, contributes to the regulation of blood pressure and to host defence. We describe in-vitro and in-vivo evidence that NO synthesis can be inhibited by an endogenous compound, NG,NG-dimethylarginine (asymmetrical dimethylarginine, ADMA). In man, this inhibitor is found in plasma and more than 10 mg is excreted in urine over 24 h. However, in patients with end-stage chronic renal failure, who have little or no urine output, elimination is blocked and circulating concentrations of the inhibitor rise sufficiently to inhibit NO synthesis. Accumulation of endogenous ADMA, leading to impaired NO synthesis, might contribute to the hypertension and immune dysfunction associated with chronic renal failure.
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PMID:Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. 134 93

The influence of endothelium on the direct contractile effects of ouabain in vascular smooth muscle was analyzed in isolated perfused guinea pig carotid arteries. After blocking the neurogenic component of the glycoside contraction with alpha-adrenergic receptor blocking drugs or treating the animals with reserpine, ouabain-induced contractions were markedly reduced in vessels with intact endothelium. However, removal of the vascular endothelium from reserpinized carotid arteries resulted in ouabain-induced contractions similar to those observed in control arteries. These effects were not mimicked by the inhibitor of nitric oxide NG-monomethyl L-arginine or by the cyclooxygenase blocker indomethacin. Bioassay experiments suggested that these endothelial effects are mediated by diffusible factors. Uptake of 86Rb to measure sodium pump activity was significantly reduced by removal of the endothelium. These results suggest the existence of an inhibitory modulation by the endothelium of contractions induced by ouabain, likely mediated by a diffusible factor (or factors) released from these cells. The nature of this substance is unknown, but it is neither related to prostaglandins nor a nitric oxide-related compound. Its mechanism of action could be the stimulation of vascular sodium pump activity, the antagonism of the pump's inhibition by ouabain, or both.
Hypertension 1992 Nov
PMID:Endothelial role in ouabain-induced contractions in guinea pig carotid arteries. 135 23

Homozygous male Brattleboro rats were given a solution of NG-monomethyl-L-arginine (L-NMMA; 1 mg ml-1) to drink for a period of 7 days. There was a persistent elevation of mean arterial blood pressure, accompanied by a significant hindquarters vasoconstriction. Within 9 h of withdrawal of L-NMMA all variables were not different from pre-L-NMMA values. Brattleboro rats (n = 3) which had been drinking NG-nitro-L-arginine methyl ester (L-NAME) solution (0.05 mg ml-1) for 5-6 months showed an increased blood pressure which reversed to normal within 48 h after withdrawing the L-NAME. Thus, inhibition of nitric oxide synthesis leads to long-lasting, but reversible, hypertension.
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PMID:Nitric oxide synthase inhibitors cause sustained, but reversible, hypertension and hindquarters vasoconstriction in Brattleboro rats. 137 33

Aortic rings from SHR are reported to have a decreased relaxation response to the endothelium-dependent agent acetylcholine compared with rings from WKY rats. Thus, a reduced EDRF (nitric oxide) response could contribute to hypertension. We found that in mesenteric small resistance arteries (200 microns I.D.) taken from 5- to 50-week old rats and mounted in a Mulvany-Halpern myograph, that the concentration-response curves to acetylcholine were similar in range and sensitivity (EC50) in arteries from SHR and WKY rats at the same age. Similarly, in small resistance arteries from human buttock skin, the relaxation to acetylcholine was not different between vessels from normotensive volunteers (mean BP = 95.2 +/- 1.5 mm Hg) and patients with untreated essential hypertension (mean BP = 116.5 +/- 2.5 mm Hg). In rabbits with chronic renovascular hypertension (cellophane renal wrap), acetylcholine and adenosine infusions into the lower abdominal aorta caused falls in hindquarter resistance that were enhanced in range, but with no change in sensitivity compared with normotensive rabbits. In normotensive rabbits, nitric oxide synthase inhibition with N omega-nitro-L-arginine infusion caused a rise in blood pressure, fall in hindquarter conductance and blockade of the acetylcholine responses. These experiments suggest that at the level of resistance arteries in vivo and in vitro, a defect in the receptor-stimulated response to EDRF associated with hypertension could not be detected. Apparently, basal nitric oxide is important in resting vasodilator tone, but its role in chronic hypertension is still unclear.
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PMID:Release of endothelium-derived relaxing factor from resistance arteries in hypertension. 137 18

Nitric oxide (NO) and atrial natriuretic factor (ANF) cause vascular relaxation by generating cyclic guanosine monophosphate (cGMP) via activation of the soluble and particulate guanylate cyclases, respectively. The chronic effects of NG-nitro-L-arginine methyl ester (L-NAME), an L-arginine antagonist and NO synthase inhibitor, on the blood pressure and plasma and aortic cGMP levels of rats were tested. Wistar rats (n = 10 per group) were given doses of L-NAME (0, 1, 5, 10, 20, 50, and 100 mg/kg.d) by gavage twice a day for 4 wk. Chronic L-NAME induced a time- and dose-dependent increase in blood pressure. The total heart weight/body weight ratio did not change in any group, despite the hypertension. The plasma levels of cGMP did not change significantly in any group, and were correlated with the plasma ANF levels (r = 0.51, P less than 0.0001). Aortic cGMP decreased in negative correlation with increasing L-NAME from 0 to 10 mg/kg.d, culminating in a 10-fold drop arterial wall cGMP. The aortic cGMP content of rats in the four highest dose groups (from 10 to 100 mg/d) tended to increase slightly and was positively correlated with endogenous ANF (r = 0.48, P less than 0.002, n = 40). Intravenous L-arginine decreased arterial blood pressure and reversed the decline in aortic cGMP. Exogenous ANF and sodium nitroprusside both significantly increased aortic cGMP. Neither the arterial wall concentrations of cGMP-dependent kinase nor cAMP was changed by L-NAME. Thus, chronic blockade of NO synthase with L-NAME induces a dose-dependent increase in blood pressure and decrease in aortic cGMP. The in vivo basal aortic cGMP seems to be mainly dependent on NO synthase: soluble guanylate cyclase activity and to a minor extent on particulate guanylate cyclase activity.
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PMID:Determinants of aortic cyclic guanosine monophosphate in hypertension induced by chronic inhibition of nitric oxide synthase. 137 15

Treatment with recombinant human erythropoietin (rHuEPO) successfully reverses anemia in uremic patients. Of major concern, however, are blood pressure (BP) increases during rHuEPO therapy, observed particularly in persons with a history of hypertension. To determine whether preexisting hypertension enhances BP increases to rHuEPO, BP responses to 2 wk of rHuEPO or placebo were observed in spontaneously hypertensive rats (SHR) and their normotensive genetic controls (Wistar-Kyoto [WKY] rats. In addition, the role of endothelial-released nitric oxide (NO) in BP alterations caused by rHuEPO through i.v. infusions of endothelium-dependent and independent vasoactive agents were indirectly examined. At trial completion, rHuEPO elevated hematocrit, hemoglobin, and mean cell volume more in SHR than in WKY rats (P less than 0.001). Despite the considerable increase in hematocrit, rHuEPO did not alter BP in either strain. An infusion of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO formation, elevated BP more in rHuEPO-treated SHR than in identically treated WKY rats (P less than 0.05). Further, the administration of L-arginine caused a greater decrease in blood pressure in SHR than in WKY rats, independent of treatment condition (P less than 0.01). Because changes in BP with endothelium-independent agents were similar across groups, responses to L-NMMA and L-arginine were specific to the endothelium and probably independent of basal BP. Thus, rHuEPO provoked greater erythropoiesis in SHR than in WKY rats but did not elevate BP. L-NMMA stimulated higher BP in SHR treated with rHuEPO, suggesting a compensatory increase in vasodilatory NO synthesis to protect against a hypertensive effect of the drug in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of erythropoietin on hematocrit and blood pressure in normotensive and hypertensive rats. 139 18

The endothelium may play a role as a target and mediator of hypertension. Due to its anatomical position, it is very exposed to mechanical forces; as a source of vasoactive material it may participate in increasing peripheral vascular resistance and in promoting local ischaemia in the heart and brain. Morphological and functional changes in the endothelium occur in experimental and human hypertension. However, the severity of the defect and the mechanisms involved among vascular beds and models of hypertension are heterogeneous. Endothelium-dependent relaxations are impaired in the aorta, carotid artery and in cerebral and mesenteric arterioles in hypertension. In the coronary circulation the defect is less pronounced. The mechanisms involve a reduced formation of nitric oxide, an enhanced production of prostaglandin H2 and an impaired responsiveness of vascular smooth muscle to nitric oxide. The role of endothelin in hypertension is controversial; circulating levels appear unaltered except in the presence of renal failure or atherosclerosis. The local vascular production of endothelin, however, may still be increased. The potentiating effects of threshold concentrations of endothelin on the vasoconstrictor response to noradrenaline are enhanced in hypertension. Thus, subtle and distinct endothelial function defects occur in hypertension, but not all vascular beds are similarly affected and different mechanisms contribute. Endothelial dysfunction may contribute to increased peripheral resistance, tissue ischaemia and cardiovascular complications.
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PMID:Heterogeneity of endothelial dysfunction in hypertension. 139 60

We examined the effect of transmural pressure on histamine-stimulated nitric oxide release from cultured endothelial cells prepared from human umbilical cord veins. PO2 and pH were kept constant throughout the experiments. Various levels of transmural pressure and atmospheric pressure (40, 80, 120 and 160 mm Hg) were applied. Nitric oxide release was inhibited in a pressure-dependent manner. The inhibitory effects were reversible, and nitric oxide had no effect on the morphology of the cells. Our results suggest that transmural pressure-mediated inhibition of nitric oxide release contributes to pressure-induced vasoconstriction and reduced endothelium-dependent relaxation in patients with hypertension.
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PMID:Transmural pressure inhibits nitric oxide release from human endothelial cells. 139 99

This study was designed to investigate the effects of L-arginine (the substrate of endothelium-derived nitric oxide) in human forearm vessels. We examined whether intra-arterial infusion of L-arginine dilated forearm vessels and augmented vasodilatory responses to acetylcholine in young, healthy humans. The left brachial artery was cannulated for drug infusions and direct measurement of arterial pressure. Forearm blood flow was measured by a strain gauge plethysmograph. Intra-arterial infusions of L-arginine at 10, 20, 40, and 60 mg/min increased forearm blood flow from 4.7 +/- 0.6 to 4.9 +/- 0.5, 5.7 +/- 0.5, 7.2 +/- 0.8, and 8.2 +/- 0.9 ml.min-1.100 ml-1, respectively (n = 8, p less than 0.01), whereas D-arginine at the same doses did not alter forearm blood flow (n = 7). Intra-arterial infusions of acetylcholine (n = 7) (4, 8, 16, and 24 micrograms/min) and sodium nitroprusside (n = 5) (0.2, 0.4, 0.8, and 1.2 micrograms/min) increased forearm blood flow dose dependently (p less than 0.01 for both). Arterial pressure was not altered with infusions of these drugs. Responses to acetylcholine were augmented with simultaneous intra-arterial infusion of L-arginine at 10 mg/ml (p less than 0.01) but not with D-arginine. Responses to sodium nitroprusside were not altered by L-arginine. These results in human forearm resistance vessels support the notion that vasodilation induced by acetylcholine is a result of the conversion from L-arginine to endothelium-derived nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Oct
PMID:Effects of L-arginine on forearm vessels and responses to acetylcholine. 139 86


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