The present study, involving 56 healthy subjects from a health screening, was undertaken to address some methodological questions regarding the measurement of endothelial function using local intra-arterial infusions of metacholine (2 and 5 micrograms min-1) to evaluate endothelium-dependent vasodilatation, and sodium nitroprusside (SNP, 5 and 10 micrograms min-1) to evaluate endothelium-independent vasodilatation. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The ratio of FBF during the highest dose of metacholine to FBF during the highest dose of SNP was used as an index of endothelial function. In 10 young volunteers the procedure was repeated after 2 h and again after 3 weeks in order to study short-term and long-term reproducibility of the method. Neither the vasodilatatory response to metacholine (r = 0.006) nor that to SNP (r = 0.08) was related to resting FBF. Neither the circumference nor the length of the arm was related to endothelial function (r = 0.01-0.11), as evaluated by the FBF on metacholine to nitroprusside ratio (mean 1.3 +/- 0.3 SD). The use of a wrist cuff to exclude hand circulation, or not, did not influence the evaluation of endothelial function significantly. Maximal FBF after 3 min of arterial occlusion of the forearm was significantly related to blood flow during both metacholine (r = 0.53, P < 0.01) and nitroprusside infusion (r = 0.36, P < 0.05), but not to the FBF on metacholine to nitroprusside ratio (r = 0.01). The short-term and long-term reproducibility of FBF during vasodilatation with metacholine and SNP was good (r = 0.89-0.97, P < 0.001), while the individual measurements for resting FBF were less reproducible when repeated after 3 weeks (r = 0.34). In conclusion, endothelial function was not related to resting FBF, nor to the arm circumference or length. No major difference was seen whether endothelial function was evaluated with or without exclusion of the hand circulation. Maximal FBF during reactive hyperaemia was not related to endothelial function.
Using both in vitro and in vivo techniques, it has repeatedly been shown that endothelium-dependent vasodilation (EDV) is impaired in different forms of experimental hypertension (SHR, Dahl salt-sensitive rat, DOCA-salt rat and renovascular hypertension). EDV has also been found to be impaired in primary, as well as in secondary forms of human hypertension. Although impaired EDV is a general finding in hypertension, the pathophysiological mechanisms might differ between different forms of hypertension and between different types of vessels and vascular beds. Impaired activity of nitric oxide synthase, increased release of endothelin-1, increased production of a prostanoid-derived contracting factor, decreased generation of endothelium-derived hyperpolarizing factor/s and impairment caused by superoxide ions have all been shown to contribute to the impairment of EDV during different conditions. While most antihypertensive treatments improve EDV in experimental hypertension, no uniform picture has been seen in human hypertension, possibly because different antihypertensive drugs have different direct actions on EDV. This review shows that while impaired EDV has been found to be a general feature of hypertension, the mechanisms involved and the therapeutic opportunities have still to be established.
1. Previous investigations have demonstrated an impaired endothelium-dependent vasodilatation (EDV) in patients with hypertension. The present study aimed to investigate if an acute rise in blood pressure to hypertensive levels impairs EDV in otherwise normotensive subjects. 2. Twenty-seven young, healthy, normotensive subjects were studied. Eight of these underwent evaluation of EDV and endothelium-independent vasodilatation (EIDV) by means of forearm blood flow measurements during local intra-arterial infusions of methacholine (2 and 4 micrograms/min) and sodium nitroprusside (5 and 10 micrograms/min), before and after 1 h of sustained hypertension, induced by noradrenaline given intravenously. Identical measurements were made in 11 subjects before and during concomitant local intra-arterial infusion of noradrenaline without change in blood pressure and eight subjects were studied during saline infusions. 3. One hour of sustained hypertension (diastolic blood pressure > 95 mmHg) significantly attenuated both forearm blood flow (17.4 +/- 6.8 versus 27.4 +/- 6.8 ml.min-1.100 ml-1 tissue at baseline, P < 0.05) and forearm vascular resistance decrease (3.2 +/- 0.87 versus 7.4 +/- 2.5 units at baseline, P < 0.05) during methacholine infusion. These attenuations were significantly more pronounced for methacholine than for sodium nitroprusside (P < 0.05). In contrast, local intra-arterial noradrenaline infusions impaired vasodilatation induced by methacholine and sodium nitroprusside to a similar extent. Saline infusions did not change either EDV or EIDV. 4. Thus, an acute rise in blood pressure to hypertensive levels induced by noradrenaline impaired EDV more than EIDV in otherwise normotensive subjects, while no such selective effect of local noradrenaline was seen, suggesting that a high blood pressure impairs endothelial vasodilator function.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.