Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Data remain insufficient to place the decreased response to L-arginine in hypertensive patients within a consistent pathophysiological sequence. The aim of the present study in patients with essential hypertension was to assess the relationships between the response to L-arginine and a set of relevant clinical and laboratory parameters. In this prospective, interventional study, we administered L-arginine to untreated hypertensive individuals and healthy control subjects and measured the clearance of inulin and of para-aminohippurate and a set of biochemical and clinical variables. L-Arginine infusion revealed major differences between control subjects and 1 subgroup (group B) of hypertensive individuals. Group B hypertensives (n=18) had no increase in inulin clearance and no decrease in renal vascular resistance with L-arginine; however, in another subset of hypertensive patients (group A, n=27), the insulin clearance increased and renal vascular resistance decreased similar to the control group (group C, n=11). The ambulatory blood pressure monitoring in group B showed both an increased mean diastolic pressure and a "nondipper" pattern in the nocturnal regulation of arterial pressure. These findings in group B were accompanied by significant alterations in optic fundus and left ventricle hypertrophy and increased microalbuminuria (all, P<0.05). Furthermore, group B individuals had significantly lower values of HDL cholesterol and a higher baseline atherogenic index, plasma insulin level, and glucose/insulin index. We disclose a previously undescribed relationship between end organ repercussion and decreased renal hemodynamic response to L-arginine. Our results may help to understand the mechanisms that lead to target organ damage in hypertension.
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PMID:Impairment of renal vasodilation with l-arginine is related to more severe disease in untreated hypertensive patients. 1164 7

The purpose of this study was to determine whether a high NaCl intake impairs endothelium-dependent and -independent vasodilation of forearm circulation in salt sensitive (SS) patients with essential hypertension. We evaluated the effects of intra-arterial acetylcholine (ACh) and isosorbide dinitrate (ISDN) on forearm hemodynamics in 29 patients with essential hypertension, while consuming a low NaCl (50 mmol/d) or high Na Cl (340 mmol/d) diet for 1 week. The forearm blood flow (FBF) was measured by strain-gauge plethysmography. Patients were classified as SS (n=12) or salt resistant (SR; n=17) based on salt-induced changes in blood pressures. The FBF responses of ACh and ISDN were similar in the SS and SR patients while on either NaCl diet, and was not altered by salt loading (ACh, SS: low NaCl 22.8+/-4.3 vs. high NaCl 21.1+/-3.6 ml/min per 100 ml, SR: low NaCl 22.5+/-4.0 vs. high NaCl 23.3+/-4.1 ml/min per 100 ml; ISDN, SS: low NaCl 13.9+/-2.1 vs. high NaCl 14.1+/-2.2 ml/min per 100 ml, SR: low NaCl 13.8+/-2.3 vs. high NaCl 14.0+/-2.2 ml/min per 100 ml). There were no significant differences in the vascular responses to ACh and ISDN in the presence of N(G)-monomethyl-L-arginine, a nitric oxide synthase inhibitor, in either group for either NaCl diet. These findings suggest that forearm resistance artery endothelial function may not be influenced by salt loading in either SS patients which finding may play a role in determining salt sensitivity in patients with essential hypertension or SR patients.
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PMID:Sodium chloride loading does not alter endothelium-dependent vasodilation of forearm vasculature in either salt-sensitive or salt-resistant patients with essential hypertension. 1176 32

Although conduit arteries develop hypertrophy after chronic NO synthesis blockade, resistance arteries remodel without hypertrophy under the same conditions. Similar findings have been described in essential hypertension. We postulated that this regional difference may be related to a heterogeneous effect of endogenous NO on proliferation along the vascular tree. Newly synthesized proteins were radiolabeled in vivo with [(3)H]L-leucine in basal conditions and during NO synthase inhibition, with or without PD98059 (inhibitor of the extracellular signal-regulated kinases [ERK] 1/2). Blocking the generation of NO by 3 different L-arginine analogues increased protein synthesis by an average of 75% in the aorta, in association with enhanced ERK 1/2 phosphorylation. PD98059 significantly reduced L-arginine analogue-induced protein synthesis and ERK 1/2 phosphorylation, confirming the involvement of ERK 1/2 as an important signaling element. In small arteries, L-arginine analogues did not influence the extent of protein synthesis, although phosphorylation of ERK 1/2 was also enhanced. To determine the role of NO in a condition of enhanced protein synthesis, angiotensin II was infused for 24 hours. Angiotensin II augmented protein synthesis in mesenteric arteries and the aorta, and was additive to NO synthase blockade in the aorta. In conclusion, endogenous NO exerts a tonic inhibitory influence on aortic growth, with limited impact on small arteries in basal and hypertrophic conditions. This heterogeneous role of NO on vascular growth may explain the heterogeneity of vascular remodeling observed in essential hypertension, a condition associated with endothelial dysfunction.
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PMID:Vessel-specific stimulation of protein synthesis by nitric oxide synthase inhibition: role of extracellular signal-regulated kinases 1/2. 1179 72

Nebivolol, a racemic mixture of (S,R,R,R) and (R,S,S,S) enantiomers, is the most beta1-selective adrenoceptor antagonist currently available for clinical use. However, its haemodynamic effects differ from those of classical beta-adrenoceptor antagonists as a result of a vasodilating action. Nebivolol is devoid of alpha-adrenergic antagonist actions, and the detailed mechanism of its vasodilator action is unknown. Nebivolol relaxes precontracted strips of canine coronary and carotid artery only if the endothelium is intact, and such relaxation is antagonized by inhibition of nitric oxide (NO) synthase, implicating the endothelial L-arginine/NO mechanism. Nebivolol and atenolol have been compared in phenylephrine preconstricted dorsal hand veins of 11 healthy men. Nebivolol caused venodilation, which was antagonized by N(G)-monomethyl-L-arginine (LNMMA), whereas atenolol did not, suggesting that such a mechanism could also operate in human veins. Venodilation could be functionally important in reducing cardiac pre-load. Beta2-adrenoceptor stimulation increases forearm blood flow (FBF) by activating the L-arginine/NO pathway but nebivolol lacks direct beta2-adrenoceptor agonist activity. Resistance vessel function has been studied by measuring FBF by venous occlusion plethysmography in healthy men during brachial artery infusions of racemic nebivolol and its enantiomers, atenolol, carbachol (a stable analogue of acetylcholine that vasodilates this vascular bed, in part by activating the L-arginine/NO pathway), nitroprusside (a NO donor that causes non-endothelium-dependent vasodilation through the same effector mechanism as endothelium-dependent agonists) and LNMMA. Nebivolol (354 microg/min) increased FBF by 91 +/- 18% (mean +/- SE, n = 8; p < 0.01), whereas an equimolar dose of atenolol had no significant effect. LNMMA inhibited responses to nebivolol and carbachol to a significantly greater extent than it reduced responses to nitroprusside. Antagonism of nebivolol by LNMMA was abolished by L-arginine. The (S,R,R,R) and (R,S,S,S) enantiomers caused similar increases of FBF. To determine whether brachial artery infusion of nebivolol causes vasodilation in the forearm resistance vasculature of patients with essential hypertension and to investigate the possible involvement of the L-arginine/NO pathway, we studied otherwise healthy volunteers with uncomplicated essential hypertension. Nebivolol (88.5, 177 and 354 microg/min, each dose for 6 min) caused similar vasodilatation as in normotensive subjects, and these responses were sensitive to inhibition by LNMMA. If acute effects of nebivolol on the L-arginine/NO pathway persist during chronic treatment of patients with hypertension or heart failure, this could reduce cardiac after-load as well as pre-load, improve organ perfusion and reduce atherogenesis and thrombosis.
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PMID:Nebivolol: endothelium-mediated vasodilating effect. 1181 87

Essential hypertension is associated with endothelial dysfunction, which is caused mainly by the production of oxygen-free radicals that can destroy nitric oxide (NO), and impair its beneficial and protective effects on the vessel wall. In prospective studies, endothelial dysfunction is associated with increased incidence of cardiovascular events. Antihypertensive drugs show contrasting effects in terms of improvement or restoration of endothelial function. Little evidence is available with beta-blockers. Whereas treatment with atenolol has a negative effect in peripheral subcutaneous and muscle microcirculation, insufficient evidence is available to establish whether new compounds such as nebivolol, which activates the L-Arginine--NO pathway, and carvedilol, which has strong antioxidant activity, can improve endothelial function in patients with hypertension. Calcium channel antagonists, particularly the dihydropyridines, can reverse impaired endothelium-dependent vasodilation in different vascular districts, including the subcutaneous, epicardial, renal and forearm circulation. However, conflicting results are found in the brachial artery. In the forearm circulation, nifedipine and lacidipine can improve endothelial dysfunction by restoring NO availability through a mechanism probably related to an antioxidant effect. ACE inhibitors, on the other hand, seem to improve endothelial function in subcutaneous, epicardial, brachial and renal circulation, whereas they are ineffective in potentiating the blunted response to acetylcholine in the forearm of patients with essential hypertension. They can also selectively improve endothelium-dependent vasodilation to bradykinin, an effect not mediated by restoring NO availability but probably related to hyperpolarisation. Recent evidence suggests angiotensin II AT(1)-receptor antagonists can restore endothelium-dependent vasodilation to acetylcholine in subcutaneous microcirculation but not in that of the forearm muscle. Evidence concerning the effect of these drugs on the brachial artery in patients with atherosclerosis is positive. However, treatment with an AT(1)-receptor antagonist can improve basal NO release and decrease the vasoconstrictor effect of endogenous endothelin-1. In conclusion, despite the considerable evidence that impaired endothelium-dependent vasodilation can be improved by appropriate antihypertensive treatment, no clinical data exist demonstrating that the reversal of endothelial dysfunction is associated with a reduction in cardiovascular events. In the near future, large scale clinical trials are required to demonstrate that treatment of endothelial dysfunction can lead to better prognosis in patients with essential hypertension.
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PMID:Effects of antihypertensive drugs on endothelial dysfunction: clinical implications. 1181 73

Adipocyte-derived leucine aminopeptidase (ALAP) inactivates angiotensin II and/or generates bradykinin in the kidney, suggesting a possible role for ALAP in the regulation of blood pressure. We considered the hypothesis that genomic variants of the ALAP gene are associated with hypertension or individual variations in blood pressure. We screened for mutations in the ALAP gene in 48 unrelated Japanese individuals and identified 33 polymorphisms including 15 novel polymorphisms. We then performed a two-stage analysis. In the first stage, the eight missense polymorphisms were evaluated for associations with blood pressure in 96 apparently healthy individuals. In the second stage, only the most promising polymorphisms were evaluated for association with essential hypertension in 143 hypertensive and 348 normotensive subjects. Among the eight missense polymorphisms, the Ile276Met and Lys528Arg polymorphisms showed significant association with blood pressure. Subsequent analysis confirmed association between the Lys528Arg polymorphism and essential hypertension. The estimated odds ratio for essential hypertension was 2.3 for presence of the Arg allele at codon 528, in comparison with presence of the Lys/Lys genotype (P = 0.004). These findings support involvement of ALAP in the regulation of blood pressure.
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PMID:Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension. 1185 41

Patients with essential hypertension have an impaired endothelium-dependent vascular relaxation in the renal arteries. The possible mechanisms by which essential hypertension is associated with alterations in endothelial function are decreased endothelial nitric oxide (NO) synthase activity, decreased availability or deficiency of L-arginine, increased endogenous NO synthase inhibitor, inactivation of NO by superoxide anions, and increased vasoconstrictors. However, the precise mechanism is not known. In addition, we are now confronted with a difficult question. And the question is whether endothelial dysfunction is a cause or consequence of hypertension. We hypothesize that the initial endothelial dysfunction raises blood pressure, and the development of hypertension impairs much more endothelial function, resulting in constituting the vicious cycle between endothelial dysfunction and hypertension. However, at the moment, it is impossible to answer this question with any certainty. Impairment of endothelial function has been shown to play a critical role in the development and maintenance of hypertension. It is clinically important to select an appropriate intervention that is effective in improving endothelial dysfunction in patients with essential hypertension. Several investigators including us have demonstrated that certain interventions improve endothelial dysfunction of forearm and renal circulation in patients with essential hypertension: angiotensin-converting enzyme inhibitors; lifestyle modification: exercise, body weight reduction, and sodium reduction; estrogen replacement in postmenopausal women; and novel properties: vitamin C and tetrahydrobiopterine. In patients with essential hypertension, endothelial function is impaired in several arteries. However, endothelial dysfunction in essential hypertension is reversible. We can restore endothelial function in essential hypertensive patients.
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PMID:Renal endothelial dysfunction and hypertension. 1187 76

The purpose of this study was to determine whether there are differences in the restoration of endothelial function by angiotensin-converting enzyme inhibition based on the severity of hypertension. Forearm blood flow (FBF) was measured in 69 patients with essential hypertension (mild, n = 23; moderate, n = 29; and severe, n = 17 randomly assigned to treatment with either imidapril or amlodipine for 24 weeks in a double-blind fashion during reactive hyperemia and after sublingual administration of nitroglycerin. Imidapril augmented the FBF response to reactive hyperemia after 24 weeks of treatment in the mild and moderate hypertensive groups, but not in the severe hypertensive group. The augmentation of the FBF response to reactive hyperemia induced by imidapril was significantly greater in the moderate hypertensive group than in the mild hypertensive group. Amlodipine did not alter the FBF response to reactive hyperemia. The increase in FBF after the sublingually administered nitroglycerin was similar in all groups. The infusion of NG-monomethyl-l-arginine, a nitric oxide synthase inhibitor, abolished the enhancement of reactive hyperemia in the mild and moderate hypertensive groups treated with imidapril. These findings suggest that the effects of imidapril on endothelial function are affected by the severity of hypertension and that angiotensin-converting enzyme inhibitor-induced augmentation of reactive hyperemia may be due to increased nitric oxide production.
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PMID:Severity of hypertension affects improved resistance artery endothelial function by angiotensin-converting enzyme inhibition. 1197 10

It is known that NO is involved in a variety of physiological functions including the regulation of blood pressure. Dysregulation of L-arginine/NOS/NO biological activity occurs in blood hypertension. The present review will focus on a significance of NO in pathogenesis of essential hypertension.
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PMID:[The role of nitric oxide in pathogenesis of essential hypertension]. 1198 89

The endothelium plays an important role in maintaining vascular tone and function. Essential hypertension is associated with alterations in endothelial function. The effects of antihypertensive agents on endothelial function have not been fully evaluated in human hypertension and data on the forearm circulation of humans are controversial. The aim of this study was to determine whether treatment with an angiotensin converting enzyme (ACE) inhibitor or a calcium antagonist improves endothelial dysfunction in hypertensive patients and whether the mechanism involved could be related to antioxidant activity. Endothelial function was estimated using venous occlusion plethysmography in 18 hypertensive patients and 11 healthy volunteers. The patients in the hypertension group were treated with enalapril or amlodipine. The change of forearm blood flow (FBF) was measured during acetylcholine infusion through the brachial artery and also during intra-arterial vitamin C infusion to explore the effects of vitamin C on responses to acetylcholine. FBF response to acetylcholine was significantly enhanced by intra-arterial infusion of vitamin C in the hypertensive group before antihypertensive treatment. Co-infusion of L-NMMA(N(G)-monomethyl-L-arginine), an inhibitor of nitric oxide synthase, blunted forearm blood flow response to acetylcholine. After antihypertensive treatment with enalapril or amlodipine for 2 months in the hypertensive group, endothelium-dependent vasorelaxation (vasodilatory response to acetylcholine) was significantly improved. Even though the mechanisms leading to depressed endothelial function in essential hypertension remain to be elucidated, our study shows that treatment with an ACE inhibitor or a calcium antagonist resulted in demonstrable improvement by a mechanism that is probably related to antioxidant activity.
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PMID:Effects of angiotensin converting enzyme inhibitor and calcium antagonist on endothelial function in patients with essential hypertension. 1213 14


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