Sodium nitroprusside alters Ca2+ flux components and Ca2(+)-dependent fluxes of K+ and Cl- in rat aorta.
1. Sodium nitroprusside (NP) caused both an inhibition of a noradrenaline (NA)-induced contraction and an elevation of cyclic guanosine 3',5'-monophosphate (cyclic GMP) in rat aorta. Both NP-induced responses were enhanced by the selective cyclic GMP phosphodiesterase inhibitor, M&B 22948 (2-o-propoxyphenyl-8-aza-purin-6-one, 30 microM). 2. The inhibition of a NA-induced contraction by NP was characterized by dissociating the intracellular Ca2+ release component from the extracellular Ca2+ influx component of the contraction. The transient contraction stimulated by NA in the absence of extracellular Ca2+ was inhibited by NP. Also, the slowly developed tension stimulated by NA in aortas depleted of stored Ca2+ and subsequently exposed to extracellular Ca2+ was inhibited by NP. Both components of contraction were equally sensitive to NP. 3. NA stimulated both unidirectional 45Ca2+ influx in the presence of extracellular Ca2+ and 45Ca2+ efflux into a 0 Ca2+ solution that contained 2 mM-ethyleneglycol-bis-(beta-aminoethylether)N,N'-tetraacetic acid (EGTA). The increased 45Ca2+ efflux is thought to reflect release of stored Ca2+ followed by membrane transport. NP greater than 10 nM inhibited both 45Ca2+ influx and release components whereas NP at 1-3 nM enhanced NA-stimulated 45Ca2+ efflux and relaxed the maintained tension caused by NA in 0 Ca2+, 2 mM-EGTA. 4. NP also inhibited the Ca2(+)-dependent 42K+ and 36Cl- effluxes from rat aorta stimulated either by NA or by high potassium. NP inhibited the contractile and flux responses to NA more effectively than the responses to high potassium. 5. These data indicate that: (1) NP reduces cytosolic Ca2+ by the combined inhibitory effects on Ca2+ influx and intracellular Ca2+ release, and by the stimulation of a Ca2(+)-ATPase; and (2) the differential sensitivity of the NA and high-potassium responses to NP may reflect underlying differences in Ca2+ handling induced by receptor occupancy and depolarization.
Department of Physiology, University of Missouri, Columbia 65212.
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D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D005292:Ferricyanides / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D011688:Purinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002712:Chlorides; D005292:Ferricyanides; D007473:Ion Channels; D011688:Purinones; D009599:Nitroprusside; D004533:Egtazic Acid; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000252:Calcium-Transporting ATPases; C011145:zaprinast; D006152:Cyclic GMP; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine