The hypotensive and
vasorelaxant effect of
dioclein in resistance mesenteric arteries was studied in intact animals and isolated vessels, respectively. 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 responses with no significant change in heart rate.
N(G)-nitro-L-arginine methyl ester (
L-NAME) did not affect the hypotensive response. In endothelium-containing or -denuded vessels pre-contracted with
phenylephrine,
dioclein (5 and 10 mg kg(-1) produced a concentration-dependent vasorelaxation (IC(50)=0.3+/-0.06 and 1.6+/-0.6 microM, respectively) which was not changed by 10 microM
indomethacin.
L-NAME (300 microM) produced a shift to the right.
Dioclein was without effect on contraction of vessels induced by physiological
salt solution (PSS) containing 50 mM KCl and the concentration dependence of
dioclein's effect on
phenylephrine induced contraction was shifted to the right in vessels bathed in PSS containing 25 mM KCl.
Tetraethylammonium (10 mM) and BaCl(2) (1 mM) increased the IC(50) for
dioclein-induced vasorelaxation without affecting the maximal response (E(max)).
Charybdotoxin (100 nM),
4-aminopyridine (1 mM) and
iberiotoxin (100 nM) increased the IC(50) and reduced the E(max).
Apamin (1 microM) reduced the E(max) without affecting the IC(50).
Dioclein produced a hyperpolarization in smooth muscle of mesenteric arteries with or without endothelium (7.7+/-1.4 mV and 12.3+/-3.6 mV, respectively). In conclusion
dioclein lowered arterial pressure probably through a decrease in peripheral vascular resistance. The underling mechanism implicated in the
vasorelaxant effect of
dioclein appears to be the opening of K(Ca) and Kv channels and subsequent membrane hyperpolarization.