Mechanisms involved in SNP‐induced relaxation and [Ca 2+ ] i reduction in piglet pulmonary and systemic arteries

We have compared the mechanisms involved in sodium nitroprusside (SNP)‐induced relaxation and [Ca 2+ ] i reduction in isolated piglet pulmonary (PA) and mesenteric (MA) arteries. SNP (10 −8   M −3×10 −5   M ) evoked a concentration‐dependent relaxation of PA and MA (pD 2 =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 [Ca 2+ ] i , expressed as the ratio of emitted fluorescence at 340 and 380 nm (F340/F380). The inhibition of the Na + /K + ‐ATPase after the incubation in a K + ‐free medium or the exposure to ouabain (10 −6   M ) inhibited SNP‐induced relaxation in MA but not in PA. SNP‐induced relaxation was not attenuated by 80 m M KCl plus nifedipine (10 −6   M ) but was inhibited by thapsigargin (2×10 −6   M ; pD 2 =5.69±0.19 and 5.89±0.19 for PA and MA, respectively). Pretreatment of PA with thapsigargin and MA with thapsigargin plus ouabain induced a stronger inhibition on the reduction in [Ca 2+ ] i than on the relaxation induced by SNP, indicating the existence of Ca 2+ ‐independent mechanisms. The activation of the Na + /K + ‐ATPase by the addition of KCl after the incubation in a K + ‐free medium similarly reduced [Ca 2+ ] i in PA and MA, whereas it relaxed with much less efficacy PA than MA. We conclude that SNP reduces [Ca 2+ ] i and causes relaxation through the activation of SERCA in PA and SERCA and Na + /K + ‐ATPase in MA. However, Ca 2+ ‐independent mechanisms also contribute to SNP‐induced effects.British Journal of Pharmacology (2001) 132 , 959–967; doi: 10.1038/sj.bjp.0703894