Search

Possible mechanisms of the inhibitory actions of sodium nitroprusside (NaNP) on histamine-induced contractile responses of isolated rabbit aorta, basilar artery and taenia coli were studied. NaNP (3 X 10(-5) M) reduced maximum contractile response to histamine in the aorta, whereas a concentration (10(-4) M) of NaNP slightly shifted the concentration-response curve for histamine towards its higher concentrations, but did not influence the maximum response in the basilar artery and taenia coli. The reduction in the maximum response of the aorta by NaNP was reversed by removal of the endothelium, or treatment with indomethacin (5 X 10(-6) M) or quinacrine (5 X 10(-6) M), but not by nordihydroguaiaretic acid (NDGA) (5 X 10(-5) M). Prostaglandin (PG) E1, PGE2 and PGI2 produced a relaxation in histamine-contracted basilar artery and taenia coli, whereas PGE1 and PGE2 produced a weak relaxation in histamine-contracted aorta. PGD2 relaxed taenia coli contracted by histamine, but had no influences in aorta and basilar artery. From these results, it is concluded that the inhibitory action of NaNP on histamine-induced contractile response in isolated rabbit aorta may be mediated at least partly by endothelium-derived arachidonic acid metabolite(s) via the cyclooxygenase pathway which must not involve PGI2. Furthermore, the difference in the inhibitory actions of NaNP between the tissues used in this study must be attributed to the absence of such mechanisms both in the basilar artery and taenia coli.

Pharmacological action of ionophore X537A was studied in taenia coli and aortic strips isolated from rabbit. These isolated smooth muscle preparations contracted by X537A (10(-5)-10(-4) M). A removal of Ca ions from the buffer solution considerably reduced the contraction of taenia coli but not that of aorta. D 600 (methoxyverapamil, 10(-6) M) was without any effect in the contraction of both tissues by X537A (10(-4) M). However, papaverine (10(-4) M) and Aspaminol (1, 1-diphenyl-3-piperidinobutanol hydrochloride, 10(-4) M) inhibited X537A (10(-4) M)-induced contraction markedly in taenia coli but slightly in aorta. Inhibitory effects of these drugs were reversed in taenia coli by increasing Ca ion concentration in buffer solution but not in aorta. X537A (10(-4) M)-induced contraction of aorta was not affected by a pretreatment of rabbit with reserpine and preincubation of the isolated preparations with guanethidine (10(-6) M) or prazosin (10(-7) M). These results suggest that ionophore X537A might produce the contraction through an increase of Ca influx in isolated rabbit taenia coli which are little or not affected by D 600, whereas the contraction of rabbit aorta induced by X537A is mainly due to facilitation of release of Ca sequestered intracellularly.

1. 1. Verapamil caused a parallel shift of the concentration-response curve for norepinephrine in rabbit thoracic aorta and the reduction in norepinephrine-induced maximum response with shifts of the concentration-response curve for norepinephrine in renal artery and portal vein. 2. 2. Diltiazem was without any effects on the response of thoracic aorta to norepinephrine, while the responses of renal artery and portal vein to norepinephrine were inhibited noncompetitively by diltiazem. 3. 3. Verapamil but not diltiazem diminished markedly dibenamine-induced inhibition of maximum response to norepinephrine in all the preparations used. 4. 4. Specific bindings of [3H]prazosin to both the membrane fractions derived from thoracic aorta and renal artery were displaced concentration-dependently by verapamil and diltiazem, but the effective concentrations of diltiazem were more than those for Ca-entry blocking activity. 5. 5. These results suggest that verapamil might antagonize norepinephrine at α1-adrenoceptors and the effective concentration for Ca-entry blocking activity of diltiazem were less than those for the interaction of diltiazem with α1-adrenoceptors.