Negative inotropic effect of carbachol on rat atria mediated by nitric oxide.
In this paper we show that isolated rat atria synthetized nitric oxide (NO) and its acts as intracellular messenger, increasing cGMP production that in turn modulates the muscarinic cholinergic dependent inhibition of contractility. Carbachol activating M2 muscarinic acetylcholine receptors (M2 mAchR) activated phosphoinositide turnover, stimulated nitric oxide synthase and increased production of NO. Inhibitors of phospholipase C, protein kinase C, calcium/calmodulin, nitric oxide synthase and guanylate cyclase activities, shifted to the right the dose-response curve of carbachol upon contractility. Moreover, sodium nitroprusside and 8-bromo cGMP, induced negative inotropic effect. These results suggest that carbachol activating M2 mAchR exerts inotropic negative effect associated to an increase production of NO. The mechanism appears to occur secondarily to stimulation of phosphoinositide turnover via phospholipase C activation. This in turn, triggers cascade reactions leading to the production of NO, that contribute to the inotropic negative action of low concentrations of carbachol.
Vila Echague
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A
CEFYBO-CONICET, Buenos Aires.
Genaro
A M
AM
Sterin-Borda
L
L
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D006325:Heart Atria / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D051381:Rats; D017208:Rats, Wistar
D002148:Calmodulin-Binding Proteins; D009569:Nitric Oxide; D002217:Carbachol; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP