title: Mechanisms involved in SNP-induced relaxation and [Ca+]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 (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.
authors.affiliation: Department of Pharmacology, Institute of Pharmacology and Toxicology (CSIC), School of Medicine, Universidad Complutense, 28040 Madrid, Spain. fperez@eucmax.sim.ucm.es
authors.forename: A L
authors.initials: AL
authors.lastname: Cogolludo
authors.forename: F
authors.initials: F
authors.lastname: Pérez-Vizcaíno
authors.forename: F
authors.initials: F
authors.lastname: Zaragozá-Arnáez
authors.forename: M
authors.initials: M
authors.lastname: Ibarra
authors.forename: G
authors.initials: G
authors.lastname: López-López
authors.forename: V
authors.initials: V
authors.lastname: López-Miranda
authors.forename: J
authors.initials: J
authors.lastname: Tamargo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000502:physiology; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D020746:Calcium Channels, L-Type; D020030:Nitric Oxide Donors; D015221:Potassium Channels; D009599:Nitroprusside; D011189:Potassium Chloride; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium