Activation of BKCa channels by nitric oxide prevents coronary artery endothelial dysfunction in ouabain-induced hypertensive rats

作者:Briones Ana M; Padilha Alessandra S; Cogolludo Angel L; Alonso Maria J; Vassallo Dalton V; Perez Vizcaino Francisco; Salaices Mercedes*
来源:Journal of Hypertension, 2009, 27(1): 83-91.
DOI:10.1097/HJH.0b013e328317a7cf

摘要

Objective Chronic-ouabain administration to rats induces hypertension and increases the endothelial modulation of vasoconstrictor responses. The aim of this study was to analyze whether ouabain-treatment affects the mechanisms involved in endothelium-dependent relaxation of coronary arteries. Methods Coronary arteries from control and ouabain-treated rats (similar to 8.0 mu g/day, 5 weeks) were used. Vascular reactivity was analyzed by isometric tension recording and membrane currents were measured using the whole-cell configuration of the patch-clamp technique. Results In 5-hydroxytryptamine (5-HT) precontracted arteries, acetylcholine ( ACh, 1 nmol/l - 10 mu mol/l) induced a similar relaxant response in coronary arteries from both groups that was abolished by the nitric oxide synthase inhibitor N-(G)- nitro-L-arginine methyl ester (100 mu mol/l). However, when arteries were contracted with high KCl ( 60 mmol/l) or preincubated with the large-conductance Ca2 -activated K (BKCa) channels-blocker iberiotoxin (0.1 mu mol/l), the relaxation elicited by ACh was more reduced in ouabain-treated than control rats. After iberiotoxin preincubation, the relaxant response of the nitric-oxide donor, DEA-NO (10 nmol/l - 100 mu mol/l) was significantly inhibited in ouabain-treated coronary arteries but not in control vessels. The soluble guanylyl cyclase activator BAY 41-2272 (10 nmol/l - 30 mu mol/l) induced relaxant responses that were inhibited by iberiotoxin. In coronary-artery myocytes isolated from ouabain-treated rats DEA-NO (1 mu mol/l) markedly increased the amplitude of the iberiotoxin-sensitive current in the whole range of test potentials, compared with nontreated rats. Conclusion Our results indicate that chronic ouabain treatment increases activation of BKCa currents by nitric oxide and this effect might contribute to preserve the endothelial function in coronary arteries in this hypertension model.

  • 出版日期2009-1