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.
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D011412:Propanolamines; D013779:Tetrodotoxin; C036089:nipradilol; D011188:Potassium; D009638:Norepinephrine; D010646:Phentolamine