The effects of 34-dihydro-8-(2-hydroxy-3-isopropylaminopropoxy)-3-nitroxy-2H-1-benzopyran (K-351) and its denitrated derivative on smooth muscle cells of the dog coronary artery.

摘要

1 Effects of 3,4-dihydro-8-(2-hydroxy-3-isopropylaminopropoxy)-3-nitroxy-2H-1-benzopyran (K-351) and its derivative, 3,4-dihydro-8-(2-hydroxy-3-isopropylaminopropoxy)-3-hydroxy-2H-1-benzopyran (K-351 (N-)) on the electrical and mechanical properties of smooth muscles of the dog coronary and mesenteric arteries were investigated, and the findings were compared with data obtained with nitroglycerin. 2 In both proximal and distal regions of the coronary arteries, K-351 and nitroglycerin reduced the resting tone and suppressed the contractions produced by high-potassium solution or by current passage to the same extent, with no remarkable change in the electrical properties of the smooth muscle membrane. 3 In the proximal regions of the descending coronary artery, low and high concentrations of noradrenaline (NA) produced relaxation and contraction of the muscle, respectively. In the distal region, NA consistently relaxed the muscle with concentrations up to 10(-5) M. In both regions, the contraction or relaxation was suppressed by phentolamine or propranolol, respectively. 4 K-351 suppressed the NA-induced contraction. K-351(N-) potentiated the NA-induced contraction and suppressed the relaxation, but these actions were weaker than those of propranolol. Nitroglycerin suppressed the NA-induced contraction and the potency was weaker than that of K-351. 5 In the mesenteric artery, K-351 depressed excitatory junction potentials, spikes and contractions evoked by perivascular nerve stimulation, while K-351(N-) potentiated or depressed mechanical responses, with no change in the electrical responses. Nitroglycerin also depressed the mechanical responses evoked by perivascular nerve stimulation with no change in the electrical responses. 6 These results suggest that K-351 has a blocking action on postjunctional adrenoceptors, and also dilator actions similar to the actions of nitroglycerin on the dog coronary artery, while K-351 (N-) possesses a weak beta-adrenoceptor blocking action.