Vascular relaxing mechanism of denopamine in isolated canine coronary, femoral, mesenteric, and renal arteries

We investigated the mechanism of vascular relaxation produced by denopamine (deno), an oral positive inotropic agent that has selective beta 1-adrenergic action. Deno concentration-dependently (0.1 microM-30 microM) relaxed ring segments of canine femoral, mesenteric, and renal arteries which were partially precontracted with 1 micron phenylephrine or norepinephrine, but did not relax those precontracted with 5 microM prostaglandin F2 alpha or 40 mM K+. The relaxation was not significantly inhibited by pretreatment with 10 microM propranolol or metoprolol. Deno produced a parallel rightward shift in concentration-response curves to phenylephrine in femoral and renal arteries. The Schild plot yielded linear regressions of slopes of 1.301 +/- 0.106 and 0.823 +/- 0.122, respectively, which were not significantly different from unity. The pA2 values of Deno against phenylephrine in femoral and renal arteries were 5.41 +/- 0.03 and 5.76 +/- 0.06, respectively. On the other hand, Deno concentration-dependently (10 nM-10 microM) relaxed ring segments of canine coronary arteries which were partially precontracted with 5 microM prostaglandin F2 alpha. The relaxation was significantly inhibited by pretreatment with 10 microM metoprolol. In conclusion, vascular smooth muscle relaxation by Deno was mediated through beta 1-adrenergic action in canine coronary arteries and through the blocking effect of alpha-adrenoceptors in canine femoral, mesenteric, and renal arteries.