Relative importance of calcium-activated potassium channels in nipradilol-induced aortic relaxation in rats

Nipradilol (CAS 81486-22-8), a vasodilatory beta-blocker, has been shown to dilate smaller vessels than nitroglycerin does, and the vasodilative effec ts of nipradilol have been reported to be less mediated by cyclic GMP (guan osine monophosphate) than those of nitroglycerin. To test the hypothesis th at cyclic GMP-independent potassium channels have a larger role in nipradil ol-induced aortic relaxation than cyclic GMP-dependent mechanisms, the effe cts of a potassium channel blocker, tetraethylammonium (TEA, CAS 56-34-8), and of a guanylate cyclase inhibitor, methylene blue (MB, CAS 61-73-4), on nipradilol-induced aortic relaxation were investigated and compared with th ose on nitroglycerin-induced aortic relaxation in isolated rat aortic rings . Relaxation response was expressed as percent relaxation, which is a perce ntage of the tension developed by 10(-7) mol/l norepinephrine. Nitroglyceri n and nipradilol similarly relaxed the aortic ring in a concentration-depen dent manner (10(-9)-10(-4) mol/l). In contrast, desnitronipradilol, a nipra dilol analogue which has no nitroxy group, induced almost no aortic relaxat ion. TEA at 10(-3) mol/l, which is selective for calcium-activated potassiu m channels, inhibited the aortic relaxation induced by nipradilol (10(-5) m ol/l) to a significantly greater extent than that induced by nitroglycerin (10(-5) mol/l) (% relaxation: 30.0 +/- 6.8 vs. 51.1 +/- 6.1 %, p < 0.05). M B (10(-5) mol/l) suppressed the relaxation by nitroglycerin slightly but no t significantly more than that by nipradilol. (% relaxation: 54.7 +/- 9.9 v s. 64.6 +/- 5.7 %). The combination of TEA and MB almost completely elimina ted the relaxation induced by nipradilol as well as by nitroglycerin. Thus, cyclic GMP-independent calcium activated potassium channels may be more in volved in the aortic relaxation by nipradilol than that by nitroglycerin in rats.