Mechanisms involved in SNP-induced relaxation and [Ca2+]i reduction in piglet pulmonary and systemic arteries

Abstract

1 We have compared the mechanisms involved in sodium nitroprusside (SNP)-induced relaxation and [Ca2+]i reduction in isolated piglet pulmonary (PA) and mesenteric (MA) arteries. 2 SNP (1078 M7361075 M) evoked a concentration-dependent relaxation of PA and MA (pD2=6.66+0.06 and 6.74+0.14, respectively) stimulated by noradrenaline, which was markedly reduced by the guanylate cyclase inhibitor ODQ. In fura 2-incubated PA and MA, SNP produced a parallel reduction in contractile force and in [Ca2+]i, expressed as the ratio of emitted ¯uorescence at 340 and 380 nm (F340/F380). 3 The inhibition of the Na+/K+-ATPase after the incubation in a K+-free medium or the exposure to ouabain (1076 M) inhibited SNP-induced relaxation in MA but not in PA. SNP-induced relaxation was not attenuated by 80 mM KCl plus nifedipine (1076 M) but was inhibited by thapsigargin (261076 M; pD2=5.69+0.19 and 5.89+0.19 for PA and MA, respectively). 4 Pretreatment of PA with thapsigargin and MA with thapsigargin plus ouabain induced a stronger inhibition on the reduction in [Ca2+]i than on the relaxation induced by SNP, indicating the existence of Ca2+-independent mechanisms. 5 The activation of the Na+/K+-ATPase by the addition of KCl after the incubation in a K+-free medium similarly reduced [Ca2+]i in PA and MA, whereas it relaxed with much less e cacy PA than MA. 6 We conclude that SNP reduces [Ca2+]i and causes relaxation through the activation of SERCA in PA and SERCA and Na+/K+-ATPase in MA. However, Ca2+-independent mechanisms also contribute to SNP-induced e ects. British Journal of Pharmacology (2001) 132, 959 ± 967 Keywords: Na+/K+-ATPase; NO; vascular smooth muscle Abbreviations: F340/F380, ratio of emitted ¯uorescence at two wavelengths of excitation (340 and 380 nm); MA, mesenteric arteries; NA, noradrenaline; PA, pulmonary arteries; PPHN, persistent pulmonary hypertension of the newborn; SNP, sodium nitroprusside; Thap, thapsigargin; SERCA, Sarcoplasmic reticulum Ca2+-ATPase