Aldosterone induces acute endothelial dysfunction in vivo in humans: evidence for an aldosterone-induced vasculopathy.
Experimental studies have suggested a role for aldosterone and glucocorticoids in the pathogenesis of endothelial dysfunction. We therefore set out to characterize the acute effects of these hormones on vascular function in vivo in normal humans. A randomized, placebo-controlled, double-blind crossover study was performed on 16 healthy male volunteers (aged 19-29 years), examining the vascular effects of acute intravenous aldosterone infusion (12 pmol.min(-1).kg(-1) for 4 h) and of oral prednisolone (single 50 mg dose). Peripheral arterial vascular function was assessed by bilateral forearm venous occlusion plethysmography using two parallel study protocols. In the first protocol, eight subjects received, successively, acetylcholine, sodium nitroprusside, noradrenaline, angiotensin I and angiotensin II. The remaining eight subjects received, successively, acetylcholine, sodium nitroprusside, verapamil and noradrenaline. Aldosterone attenuated endothelium-dependent vasodilatation to acetylcholine as compared with either prednisolone or placebo (maximum vasodilatation: placebo, 357+/-38%; aldosterone, 257+/-21%; P <0.05). However, background endothelium-independent vasodilatation was not affected by either aldosterone or prednisolone. There were also no significant changes in vasoconstriction induced by angiotensin or noradrenaline following aldosterone or prednisolone treatment compared with placebo. Blood pressure and baseline blood flow did not differ between any of the study phases. Thus acute short-term systemic administration of aldosterone results in endothelial vasodilator dysfunction in normal men, providing evidence for an aldosterone-induced vasculopathy, which may be particularly relevant not only in heart failure but also in hypertensive patients with high aldosterone/renin ratios.
Farquharson
Colin A J
CA
University Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
Struthers
Allan D
AD
D000328:Adult; D000450:Aldosterone / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005542:Forearm / Q000098:blood supply; D005938:Glucocorticoids / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D010991:Plethysmography; D011239:Prednisolone / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D005938:Glucocorticoids; D014665:Vasodilator Agents; D000450:Aldosterone; D011239:Prednisolone