| Abstrakt: |
We investigated the mechanism of vascular relaxation by denopamine (Deno), an oral positive inotropic agent that has selective β1-adrenergic action. Deno relaxed, dose-dependently (0.1–30 μM), ring segments of rabbit aorta, which were partially precontracted with 1 μMphenylephrine (Phe) or norepinephrine (NE). but did not relax those precontracted with 5 μMprostaglandin F2αor 40 mMK+. The relaxation was not significantly inhibited by pretreatment with 10 μMpropranolol or metoprolol. Deno produced parallel shifts in concentration–response curves to Phe, but this was not true for clonidine. The Schild plot analysis resulted in a linear regression of a slope of 1.075 ± 0.063. which was not significantly different from unity, and the pA2value of Deno against Phe was 5.57 ± 0.02. The specific binding of [3H]prazosin to a rabbit aorta membrane preparation was displaced in a concentration-dependent manner by the simultaneous addition of Deno. The slope of a Hill plot was not significantly different from unity (1.102 ± 0.147). The pK1value for Deno calculated from the displacement curve was 5.29 ± 0.17, which was not significantly different from the pA2value of Deno. In conclusion, vascular smooth muscle relaxation by Deno was mediated by the blocking effect of α1-adrenoceptors. Thus, these findings suggest that Deno may he effective in the treatment of congestive heart failure because it elicits a positive inotropic effect by β1-adrenergic action and vasodilation by α1-adrenergic blocking action. |
