Pharmacological evidence for the activation of potassium channels as the mechanism involved in the hypotensive and vasorelaxant effect of dioclein inrat small resistance arteries

1 The hypotensive and vasorelaxant effect of dioclein in resistance mesente ric arteries was studied in intact animals and isolated vessels, respective ly. 2 In intact animals, initial bolus administration of dioclein (2.5 mg kg(-1 )) produced transient hypotension accompanied by an increase in heart rate. Subsequent doses of dioclein (5 and 10 mg kg(-1)) produced hypotensive res ponses with no significant change in heart rate. N-G-nitro-L-arginine methy l ester (L-NAME) did not affect the hypotensive response. 3 In endothelium-containing or -denuded vessels pre-contracted with phenyle phrine, dioclein (5 and 10 mg kg(-1) produced a concentration-dependent vas orelaxation (IC50 = 0.3 +/- 0.06 and 1.6 +/- 0.6 muM, respectively) which w as not changed by 10 muM indomethacin. L-NAME (300 muM) produced a shift to the right. 4 Dioclein was without effect on contraction of vessels induced by physiolo gical salt solution (PSS) containing 50 mM KCI and the concentration depend ence of dioclein's effect on phenylephrine induced contraction was shifted to the right in vessels bathed in PSS containing 25 mM KCl. 5 Tetraethylammonium (10 mM) and BaCl2 (1 mM) increased the IC50 for diocle in-induced vasorelaxation without affecting the maximal response (E-max). C harybdotoxin (100 nM), 4-aminopyridine (1 mM) and iberiotoxin (100 nM) incr eased the IC50 and reduced the E-max. Apamin (1 muM) reduced the E-max with out affecting the IC50. 6 Dioclein produced a hyperpolarization in smooth muscle of mesenteric arte ries with or without endothelium (7.7 +/- 1.4 mV and 12.3 +/- 3.6 mV, respe ctively). 7 In conclusion dioclein lowered arterial pressure probably through a decre ase in peripheral vascular resistance. The underling mechanism implicated i n the vasorelaxant effect of dioclein appears to be the opening of Kc, and Ky channels and subsequent membrane hyperpolarization.