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  • Title: Mechanisms involved in SNP-induced relaxation and [Ca+]i reduction in piglet pulmonary and systemic arteries.
    Author: Cogolludo AL, Pérez-Vizcaíno F, Zaragozá-Arnáez F, Ibarra M, López-López G, López-Miranda V, Tamargo J.
    Journal: Br J Pharmacol; 2001 Feb; 132(4):959-67. PubMed ID: 11181438.
    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 (10(-8) M-3x10(-5) 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 fluorescence 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 (10(-6) M) inhibited SNP-induced relaxation in MA but not in PA. SNP-induced relaxation was not attenuated by 80 mM KCl plus nifedipine (10(-6) M) but was inhibited by thapsigargin (2x10(-6) 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 efficacy 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 effects.
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