Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial dysfunction may be related to cardiovascular risk factors, such as aging, hypertension, and atherosclerosis. We investigated whether aging and hypertension independently alter endothelial function in the renal circulation in humans in the absence of abnormalities in lipid and glucose metabolism. L-Arginine (500 mg/kg over 30 minutes) was intravenously administered to 33 patients with essential hypertension and 35 normotensive subjects. The L-arginine-induced increases in renal plasma flow (10.1+/-0.8% versus 15.8+/-0.9%, P<.05) and plasma cGMP (53+/-4% versus 82+/-5%, P<.05) were significantly smaller in patients with essential hypertension than in the normotensive subjects. Multivariate stepwise regression analysis showed that age (P<.0002) and the mean blood pressure (P<.0001) were independently and negatively correlated with the renal plasma flow response to L-arginine. Age (P<.002), mean blood pressure (P<.0001), and male sex (P<.05) were independently correlated with the L-arginine-induced increase in plasma cGMP. The peak change in plasma cGMP was significantly correlated with the L-arginine-induced increase in renal plasma flow (r=.63, P<.001). These findings suggest that aging and hypertension may independently impair endothelium-dependent renovascular dilation and that this effect may be caused at least in part by a decrease in nitric oxide production.
Hypertension 1997 Aug
PMID:Aging and severity of hypertension attenuate endothelium-dependent renal vascular relaxation in humans. 926 Sep 89

Endothelial dysfunction is a prevalent phenomenon in non-insulin dependent diabetic (NIDDM) patients with hypertension and albuminuria, and may contribute to the development and progression of cardiovascular disease, which is the main cause of the high morbidity and mortality observed in these patients. Therefore the aim of our study was to evaluate whether inhibition of angiotensin-converting enzyme (with lisinopril 10-20 mg day-1) could ameliorate endothelial dysfunction more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg day-1), usually in combination with a diuretic. We performed a 12-month prospective, randomized, double-blind, parallel study in 43 hypertensive NIDDM patients with diabetic nephropathy (21 treated with lisinopril and 22 with atenolol). The following variables were measured: 24-h ambulatory blood pressure (ABP); transcapillary escape rate of albumin (TERalb; i.e. initial disappearance of intravenously injected 125I-labelled human serum albumin); serum concentrations of von Willebrand factor (vWF), using ELISA, and urinary albumin excretion rate (UAE). Data are presented for 32 patients (16 lisinopril and 16 atenolol; age 60 years, SD 8; 25 males) out of 35 who completed the study and had valid measurements of TERalb. At baseline the two groups were comparable; TERalb (8.5 (SEM 0.6) vs. 7.2 (0.4)%); vWF (2.09 (range 0.82-4.34) vs. 1.97 (0.95-3.86) IU ml-1; UAE 916 (x/divided by antilog SEM 1.3) vs. 1444 (1.2), and mean ABP 110 (SEM 3) vs. 113 (2) mmHg, in the lisinopril and atenolol group, respectively. During follow up, the mean ABP was equally reduced in the lisinopril and atenolol group, by 12 (SEM 2) vs. 10 (2) mmHg, respectively, TERalb decreased in the lisinopril group by 0.6 (SEM 0.7)%, whereas it increased in the atenolol group 1.5 (0.5)%; the mean difference was 2.2% (95% CI, 0.5 to 3.9; p = 0.015). UAE was reduced by 45% (95% CI, 25 to 60) in the lisinopril group vs. 10% (-15 to 30) in the atenolol group (p = 0.014). Serum vWF was not changed during follow up in either group. Our study suggests that lisinopril has both reno- and vasculoprotective properties in hypertensive NIDDM patients with diabetic nephropathy.
 ...
PMID:Lisinopril improves endothelial dysfunction in hypertensive NIDDM subjects with diabetic nephropathy. 927 69

Significant new findings in the last decade have demonstrated that the vascular endothelium is an important regulatory organ in maintaining cardiovascular homeostasis and that endothelial dysfunction is present in several cardiovascular diseases. With the production of multiple vasoactive substances the normal endothelium modulates the tone of the underlying vascular smooth muscle. These include endothelium-derived relaxing factors such as prostacyclin (PG1(2)), nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) and vasoconstrictors such as endothelin-1 and angiotensin II. The antiplatelet, antithrombotic and antifibrinolytic properties of the normal endothelium contribute to the maintenance of the fluidity of the blood. Activation or injury to the endothelial cells disrupts the function of the endothelial cells leading to the development of endothelial dysfunction. Endothelial dysfunction is accompanied by vasospasm, thrombosis, and atherosclerosis. It is present in cardiovascular diseases such as hypertension, atherosclerotic heart diseases, congestive heart failure and many others. It has been shown that some therapeutic effects of drugs such as angiotensin-enzyme inhibitors is in part due to the overcoming of endothelial dysfunction.
 ...
PMID:The endothelium in health and in cardiovascular disease. 928 90

Endothelial dysfunction has been documented both in the forearm and coronary beds of essential hypertensive patients. Impairment in the tonic release of nitric oxide (NO) is secondary to hypertension, while the alteration in agonist-induced endothelium-dependent vasodilation seems to be a primary defect caused both by an alteration of the L-arginine-NO pathway and the production of cyclooxygenase-dependent EDCFs, such as prostanoids or superoxide anions. These latter substances curtail endothelium-dependent vasodilation mainly by inactivating NO production. Although experimental data clearly indicate that the L-arginine-NO pathway participates in the regulation of renal hemodynamics and renal excretory function under basal and stimulated conditions, data in humans are scanty and confounded by methodological approaches. A posteriori interpretation of data obtained with intrarenal infusion of acetylcholine in kidney donors suggests that endothelium dependent vasodilation in the kidney is impaired by aging, a phenomenon well documented in the forearm and coronary circulation. Systemic infusion of L-arginine induced renal vasodilation and natriuresis in normotensive subjects, an effect which seems to be mediated mainly by intrarenal NO production. Moreover the few available data suggest that both renal vasodilation and renal production of NO in response to L-arginine are blunted in patients with essential hypertension and that superoxide anions, may be, at least partially, responsible for this alteration of the L-arginine-NO pathway. In conclusion, endothelial dysfunction has been well documented in the forearm and coronary circulation of patients with essential hypertension. Available data suggest that endothelial, dysfunction is also detectable in the kidney and that a common mechanism, probably superoxide anions, can account for this abnormality.
 ...
PMID:Endothelial function in hypertension. 937 26

Endothelial dysfunction is recognized as the initial step in the atherosclerotic process. To date, most interventions attempting to improve endothelial dysfunction have targeted one or more of the numerous risk factors that can cause endothelial damage: hypertension (angiotensin-converting enzyme inhibitors and calcium antagonists), hypercholesterolemia (lipid-lowering agents), cigarette smoking (cessation), sedentary lifestyle (increased physical activity), menopause (estrogen replacement therapy), and diabetes mellitus (control of associated metabolic abnormalities). Interventions targeted specifically to the endothelium remain speculative, as the precise mechanisms of endothelial dysfunction are still being elucidated. Several pharmacologic agents have been suggested to achieve vascular protection through mechanisms that go beyond their primary therapeutic (e.g., hypotensive or hypocholesterolemic) actions; examples of these are angiotensin-converting enzyme inhibitors or HMG-CoA reductase inhibitors. Beneficial changes to the endothelium might result from promotion of vasorelaxation, inhibition of vasoconstriction, reduction in the production of free radicals, or other mechanisms that protect the endothelium from injury.
 ...
PMID:Therapeutic interventions in endothelial dysfunction: endothelium as a target organ. 942 52

The generation of nitric oxide by the vascular endothelium maintains a continuous vasodilator tone that is essential for the regulation of blood flow and blood pressure. Nitric oxide also contributes to the control of platelet aggregation and has important antiatherogenic effects. These properties are mediated by the action of constitutive nitric oxide synthase and subsequent activation by nitric oxide of soluble guanylate cyclase. Impaired release of nitric oxide occurs in most animal and human models of hypertension, contributing to the increased peripheral resistance and most likely to the development of cardiovascular complications. Antihypertensive medications (angiotensin-converting enzyme [ACE] inhibitors and calcium channel blockers) appear to prevent the impairment of nitric oxide-mediated vasodilation in experimental hypertension, though in humans the data are not as clear. Reduced nitric oxide release appears therefore to be a consequence rather than a cause of high blood pressure, and the reduction in blood pressure per se is most important. In hyperlipidaemia, endothelium-dependent relaxations are reduced probably due to the inhibitory action of oxidized low-density lipoproteins on endothelium-dependent relaxations. Lipid-lowering strategies and, more recently, ACE inhibition have been demonstrated to improve nitric oxide dependent coronary vasodilation in hypercholesterolaemic patients with and without atheromatous coronary disease. Nitric oxide dependent vasodilation is also impaired in insulin- and non-insulin-dependent diabetes as well as in healthy aging. Endothelial dysfunction may be improved in non-insulin-dependent diabetes by administration of the antioxidants, supporting the hypothesis that nitric oxide inactivation by oxygen-derived free radicals contributes to abnormal vascular reactivity in diabetes.
 ...
PMID:Impairment and restoration of nitric oxide-dependent vasodilation in cardiovascular disease. 948 1

The vascular endothelial cell is a multipotent cell which has several functions: transport barrier, phagocytosis, coagulation/anticoagulation, fibrinolysis, autocrine/paracrine and metabolic functions. The release of vasoactive agents, such as the vasodilators EDRF (NO) and EDHF, and vasoconstrictors, such as endothelin (ET), represents an important local mechanism altering the balance of vasodilation/ vasoconstriction of the vascular smooth muscle cell. Inhibition of the synthesis of NO by exogenous (e.g. L-NAME) or endogenous (e.g. ADMA) L-arginine analogues may cause transient or sustained hypertension. A similar effect may be achieved by continuous administration of the potent vasoconstrictor ET. Endothelial dysfunction, associated with a deficient NO production and release as well an enhanced ET generation, may be present in some forms of vascular disease, such as hypertension, atherosclerosis, diabetes mellitus or sleep apnea. Whether such alterations may be a cause of hypertension and involved in the maintenance of high blood pressure or whether they represent a consequence of the hypertensive disease remains to be concluded. Furthermore, while there is emerging evidence that endothelial dysfunction in cardiovascular disease may be reversed by therapy, it remains to be determined whether measures of endothelial function in man may serve as predictors for morbidity or mortality.
 ...
PMID:Measures of endothelial function as an endpoint in hypertension? 949 29

Endothelial dysfunction is a key feature of diabetes mellitus and is thought to be the major cause of vascular complications associated with the disease. The vascular endothelium demonstrates impaired synthesis of vasodilators and increased release of procoagulants and vasoconstrictors, defects which theoretically could explain the increased incidence of atherosclerosis and hypertension found within this patient group. The pathways mediating endothelial cell layer dysfunction are unknown, although many candidates have been proposed. This review concentrates on the hypothesis that increased oxidative stress combined with abnormal plasma lipid composition leads to reduced synthesis of endothelial vasodilators and hence endothelial dysfunction. Free radical generation is undoubtedly raised in diabetes but the evidence for decreased antioxidant status is debatable. The role of antioxidant and lipid-lowering therapy is considered, but few studies have directly investigated the effect of treatment on vascular function. Concern arises from individual studies of vitamin E in diabetic animals which have proved deleterious. Current literature implies that a combination therapy of vitamin E and vitamin C may be beneficial, but this needs to be investigated further in both animal and human diabetes.
 ...
PMID:Oxidative stress and lipids in diabetes: a role in endothelium vasodilator dysfunction? 954 38

The vascular endothelium controls vasomotor tone by releasing a number of substances like nitric oxide (NO). NO has been shown to play a very important role, because it mediates vasodilation and furthermore inhibits platelet aggregation, expression of adhesion molecules for monocytes and adhesion of neutrophils and it impairs growth of vascular smooth muscle cells. An increased oxidative stress, decreasing the bioavailability of NO, is mainly responsible for a blunted endothelium dependent vasoreactivity. Risk factors for endothelial dysfunction are coronary artery disease, hypertension, hypercholesterolemia, smoking, and aging. Endothelial dysfunction in the presence of these risk factors might contribute to the occurrence of myocardial ischemia, aggravate acute coronary syndromes and accelerate progression of coronary artery disease. Amelioration of blunted endothelial function appears to be a major therapeutical goal to reduce ischemia and clinical events and might even retard progression of coronary artery disease.
 ...
PMID:[The role of endothelial function for ischemic manifestations of coronary atherosclerosis]. 959 5

Nitric oxide (NO) is the main agent of communication between the endothelium and the smooth muscle, involved in vasodilatation. Its vasodilator action requires prior tonic contraction of smooth muscle cells, related to vasoactive agents such as catecholamines or angiotensin II-induced centripetal communications and pharmaco-mechanical coupling. In physiological conditions, NO is liberated following constitutive endothelial NO synthase activity in response to shear stress generated by the dynamics of blood on the arterial wall. Endothelial dysfunction modifying NO production is implicated in different cardiovascular diseases such as hypertension, congestive heart failure and atherosclerosis.
 ...
PMID:[Role of endothelial nitric oxide in the regulation of arterial tone]. 961 14


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>