Mode of action of sodium nitroprusside on vascular smooth muscle.
1. Sodium nitroprusside is a potent relaxant of smooth muscles with a predominantly tonic response, e.g. rat aorta contracted by noradrenaline, angiotensin II, Phe2-Lys8-vasopressin, BaC1(2), or KC1, and guinea-pig tracheal smooth muscle contracted by carbachol. 2. Smooth muscle preparations from the splanchnic region and with varying degrees of phasic contractility are less sensitive and develop tachyphylaxis (portal vein, duodenum of the rat) or are unresponsive to sodium nitroprusside (vas deferens, uterus of the rat). 3. Cardiac auricles of the guinea pig are not affected by sodium nitroprusside in either frequency or amplitude or spontaneous contractions. 4. Sdium nitroprusside causes a parallel shift of the dose-response curve of rat aorta to noradrenaline to the right and reduces the maximum response. 5. The drug has no blocking or stimulant effect on alpha- or beta-adrenoceptors, respectively. 6. Sodium nitroprusside inhibits the contractile response of calcium-depleted depolarized rat aorta to extra-cellular calcium. Like verapamil, it inhibits the increment in 45calcium uptake of rabbit aorta elicited by K+. Sodium nitroprusside significantly reduced 45calcium binding by microsomes prepared from rabbit aorta. 7. Rabbit aorta was incubated with lanthanum chloride to prevent calcium influx; sodium nitroprusside reduced the maintained rapid contraction phase in response to noradrenaline which is believed to be based on the intracellular activation of calcium. 8. In rat aorta, cellular cAMP and ATP levels were not found to be affected by the drug. 9. Rabbit aorta, "skinned" by glycerination is unresponsive to sdoium nitroprusside. 10. It is concluded that sodium nitropruside acts on exictation-contraction coupling predominantly in tonic smooth muscle by interfering with both the influx and the intracellular activation of calcium.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002132:Calcium Radioisotopes; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005292:Ferricyanides / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D008861:Microsomes / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects
D002132:Calcium Radioisotopes; D005292:Ferricyanides; D011941:Receptors, Adrenergic; D009599:Nitroprusside; D007811:Lanthanum; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D002118:Calcium; D009638:Norepinephrine