Regular Aerobic Exercise Augments Endothelium-Dependent Vascular Relaxation in Normotensive As Well As Hypertensive Subjects

Abstract

Background-Several nonpharmacological interventions, including exercise, are recommended in primary prevention of hypertension and other cardiovascular diseases in which the pathogenetic role of endothelial dysfunction has been suggested. We studied the effects of long-term aerobic exercise on endothelial function in patients with essential hypertension. Methods and Results-The forearm blood flow was measured by strain-gauge plethysmography. The responses of forearm vasculature to acetylcholine were smaller in the hypertensive patients than in the normotensive subjects. There was no significant difference in forearm vascular responses to isosorbide dinitrate in the normotensive and hypertensive subjects. We evaluated the effects of physical exercise for 12 weeks on forearm hemodynamics in untreated patients with mild essential hypertension who were divided randomly into an exercise group (nϭ10) and a control group (nϭ7). After 12 weeks, the forearm blood flow response to acetylcholine increased significantly, from 25.8Ϯ9.8 to 32.3Ϯ11.2 mL ⅐ min Ϫ1 ⅐ 100 mL tissue Ϫ1 (PϽ0.05), in the exercise group but not in the control group. The increase in the forearm blood flow after isosorbide dinitrate was similar before and after 12 weeks of follow-up in both groups. The infusion of N G -monomethyl-L-arginine abolished the exercise-induced enhancement of forearm vasorelaxation evoked by acetylcholine in the exercising group. In normotensive subjects also, long-term aerobic exercise augmented acetylcholine-stimulated nitric oxide release. Conclusions-These findings suggest that long-term physical exercise improves endothelium-dependent vasorelaxation through an increase in the release of nitric oxide in normotensive as well as hypertensive subjects. (Circulation. 1999;100:1194-1202.)

Endothelial dysfunction and hypertension in aging

“…[23][24][25][26] The simple molecule NO regulates basal vascular tone, at least in part, by about 50% in the brachial artery in humans. 11,26 Thus, loss of healthy endothelial function becomes a trigger of atherosclerosis. Endothelial dysfunction is the initial step in the pathogenesis of arteriosclerosis, resulting in cardiovascular complications.…”

“…Endothelial function is restored by appropriate interventions, including pharmacological therapy, such as renin-angiotensin system inhibitors and statins, supplementation therapy and lifestyle modifications. 11,[31][32][33][34][35] ASSESSMENT OF ENDOTHELIAL FUNCTION In experimental studies, methods for assessment of endothelial function have been established by using a ring experiment protocol, endothelial functional alteration in expression of transcriptional factors and genes and genetic ablation of endothelial NO synthase (eNOS) in animal models. 36,37 It is clinically important to estimate the degree of endothelial dysfunction.…”

“…Recently, several investigators, including us, have evaluated the effects of intra-arterial infusion of NO agonists, such as acetylcholine, methacholine and bradykinin, and intra-arterial infusion of NO antagonists on forearm blood flow using a mercury-filled Silastic strain-gauge plethysmography and the effects on coronary blood flow using a Doppler flow guide wire. [9][10][11]17,26,27,35 The responses to intraarterial infusion of vasoactive agents should be most suitable for assessing endothelial function, because the use of agonists to stimulate NO release and the use of antagonists of NO allow us to draw more specific conclusions concerning the role of basal and stimulated NO release. However, the invasive methods are time consuming and are a burden for patients.…”

“…37 In hypertensive patients also, endothelium-dependent vascular relaxation in coronary, forearm and renal arteries was found to be impaired, and endothelial dysfunction, which is involved in the development of atherosclerosis, was found to increase the risk of cardiovascular and cerebrovascular diseases. [9][10][11][12][13][14][15]27,35 As Panza et al 9 reported for the first time in 1990 that the dose-response curve obtained by acetylcholine in patients with hypertension was smaller than the curve in normal controls and that the dose-response curves obtained by sodium nitropreside were similar in the two groups, suggesting that endothelial function, but not smooth muscle function, is selectively impaired in patients with hypertension, a large number of studies have shown that hypertension is associated with endothelial dysfunction.…”

“…8 A great number of studies have shown that aging and hypertension are associated with impairment of endothelium-dependent vascular relaxation in coronary, forearm and renal arteries, and endothelial dysfunction, which is involved in the development of atherosclerosis, was found to increase the risk of cardiovascular and cerebrovascular diseases. [9][10][11][12][13][14][15][16][17] It is expected that improvement or augmentation of endothelial function will prevent the development of atherosclerosis, resulting in reduction in cardiovascular and cerebrovascular events.…”