Effects of 3,4-dihydro-8-(2-hydroxy-3-isopropylaminopropoxy)-3-nitroxy-2H-1-bezopyran (K-351) on smooth muscle cells and neuromuscular transmission in guinea-pig vascular tissues.

The effects of 3,4-dihydro-8-(2-hydroxy-3-isopropylaminopropoxy)-3-nitroxy-2H-1-benzopyran (K-351) on vascular smooth muscle cells and neuromuscular transmission were investigated by the microelectrode and mechanographic methods using intact and skinned smooth muscles from guinea pigs. K-351 markedly inhibited the norepinephrine-induced contraction and slightly reduced the K-induced contraction in the mesenteric artery, but did not affect the acetylcholine-induced contraction in the coronary artery. K-351 inhibited the contraction evoked by perivascular nerve stimulation to a greater extent than that evoked by exogenously applied norepinephrine in the pulmonary artery. However, these sequences were reversed in the mesenteric artery. In the mesenteric artery, K-351 (6 x 10(-7) M) suppressed and phentolamine (10(-6) M) enhanced the contraction evoked by perivascular nerve stimulation, at frequencies over 1.0 Hz. In the mesenteric artery, K-351 did not affect the spike evoked by an outward current pulse or the spike on the excitatory junction potential; in the portal vein, it did increase spontaneously generated spikes due to depolarization of the membrane. In the skinned mesenteric artery, K-351 did not modify the amplitude of Ca-induced contraction. The excitatory junction potential evoked by perivascular nerve stimulation (0.1-1.0 Hz) was markedly inhibited by K-351 with no effect on the facilitation process, whereas phentolamine enhanced both excitatory junction potentials and the facilitation process. These findings indicate that K-351 inhibited mainly intra- and extrajunctional alpha adrenoceptors and, as the former was not affected by phentolamine or prazosin, the action of this new agent differs from the actions of heretofore available alpha-1 and alpha-2 adrenoceptor antagonists.