Influence of acute and chronic mineralocorticoid excess on endothelial function in healthy men.
Aldosterone has rapid nongenomic effects in the human vasculature. However, data are not uniform and little is known about chronic effects of aldosterone. Therefore, we investigated acute and chronic effects of elevated aldosterone levels on endothelial function in the forearm vasculature of healthy men. In a first crossover study, the effects of arterial aldosterone infusion in ascending doses (3.3 to 55 pmol/min per 1000 mL forearm volume) on forearm blood flow were investigated in 8 healthy men (26+/-2 years). In a second study, endothelium-dependent (acetylcholine; 0.08, 0.275, and 2.75 micromol/min per 1000 mL) and endothelium-independent (sodium nitroprusside 0.02 micromol/min per 1000 mL) vasodilation and basal nitric oxide formation (forearm blood flow response to blockade by N(G)-monomethyl-l-arginine 8 micromol/min per 1000 mL) were tested in 10 healthy men (age 30+/-5 years) at baseline, during infusion of 55 pmol/1000 mL per min aldosterone (acute effects), and after 0.3 mg/d oral fludrocortisone for 2 weeks (chronic effects) on separate days. Forearm blood flow was assessed by venous occlusion plethysmography. No change in forearm blood flow was seen with aldosterone infusion alone. Acute coinfusion of aldosterone increased vasodilation to sodium nitroprusside by 93% (P<0.01) and to acetylcholine by 60% (P=0.14). Response to N(G)-monomethyl-l-arginine did not change. After 2 weeks of oral fludrocortisone, response to acetylcholine was enhanced by 72% compared with baseline (P=0.03). Additionally, response to N(G)-monomethyl-l-arginine was enhanced by 80% compared with baseline (P=0.05). Aldosterone acutely enhances vasodilation to exogenous nitric oxide whereas mineralocorticoid excess for 2 weeks enhances basal nitric oxide bioactivity and improves endothelium dependent, nitric oxide-mediated vasodilation in the forearm vasculature of healthy men.
Nietlispach
Fabian
F
Clinic of Cardiology, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.
Julius
Barbara
B
Schindler
Ruth
R
Bernheim
Alain
A
Binkert
Christoph
C
Kiowski
Wolfgang
W
Brunner-La Rocca
Hans Peter
HP
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000284:Administration, Oral; D000328:Adult; D000450:Aldosterone / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D001916:Brachial Artery; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005438:Fludrocortisone / Q000008:administration & dosage / Q000494:pharmacology; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000450:Aldosterone; D000109:Acetylcholine; D005438:Fludrocortisone