Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension.

Abstract

In isolated blood vessels, acetylcholine releases endothelium-derived relaxing factor (EDRF). In vivo, the vasodilator action of acetylcholine may be mediated by EDRF, but prostacyclin or prejunctional inhibition of adrenergic neurotransmission may also be involved. Therefore, we investigated whether acetylcholine releases EDRF in humans in vivo and, if so, whether the response altered in essential hypertension. Acetylcholine was infused into the brachial artery, and forearm blood flow measured by venous occlusion plethysmography. In control subjects, acetylcholine (0.02-16 micrograms/min/100 ml tissue) increased flow from 2.4 +/- 5.0 to 20.6 +/- 5.2 ml/min/100 ml tissue (n = 14; p less than 0.05) and decreased forearm vascular resistance from 42.0 +/- 4.1 to 6.0 +/- 1.4 units (p less than 0.03), a response comparable to that of sodium nitroprusside (0.6 micrograms/min ml tissue). Acetylsalicylic acid (500 mg i.v.) given to block vascular prostacyclin production did not alter the response (n = 14). alpha-Adrenoceptor blockade by phentolamine (12 micrograms/min/100 ml tissue) did not prevent the increase in flow evoked by acetylcholine. In hypertensive patients, the decrease in forearm vascular resistance induced by acetylcholine but not evoked by sodium nitroprusside was reduced as compared with controls (14.5 +/- 3.1 and 6.1 +/- 1.6 units, respectively; n = 8; p less than 0.05). Thus, the vascular effects of acetylcholine in the human forearm circulation are independent of prostaglandins and adrenergic neurotransmission and therefore are most likely to be mediated by EDRF; the acetylcholine-induced release of EDRF is blunted in patients with essential hypertension.

Endothelial dysfunction in cardiovascular disease and Flammer syndrome—similarities and differences

“…In contrast, pharmacological agents (e.g., acetylcholine) are administered by intra-arterial infusion in a dose-dependent manner to test vasoreactivity of the brachial artery. The other forearm serves as internal control due to minimal systemic effect of the infusion [42]. Generally, FMD and plethysmography are better suited for serial or longitudinal studies than between-group testing due to interindividual variability [43].…”

Endothelial dysfunction and hypertension in aging

“…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.…”

The haemodynamic response to hyperinsulinaemia in hypertensive subjects

“…14,15 It has previously been shown that endothelium-dependent vasodilatation is impaired in hypertensive subjects. 16,17 It therefore seems likely that a defect in the NO-system plays a role in the blunted effect of insulin on TPRI seen in this sample of hypertensive subjects.…”