Nitric oxide has no chronotropic effect in right atria isolated from rat heart.
This study was designed to determine if nitric oxide (NO) has direct effects on heart rate or if it is involved in the chronotropic actions of adrenergic or cholinergic stimulation. Right atria were isolated from hearts of adult male rats, bathed in Krebs-Henseleit buffer (37 degrees C), and used to monitor spontaneous rate. For comparison, ring segments of thoracic aorta were also suspended in the Krebs-Henseleit solution and used to examine vascular actions of various agents. The dose-dependent chronotropic effects of acetylcholine (10(-7)-10(-3) M) and norepinephrine (10(-8)-3 x 10(-4) M) in right atria were not affected by pretreatment with 10(-4) M N-nitro-L-arginine or 10(-3) M N-nitro-L-arginine-methyl ester, inhibitors of L-arginine-derived NO production. SIN-1 (3-morpholino-sydnonimine), an agent which releases NO in aqueous solution, elicited a dose-dependent (0.3-100 microM) vasorelaxation in aortic preparations constricted with 60 mM KCl; the ED50 value for this effect was increased by pretreatment with methylene blue (10 microM) and LY-83,583 (6-(phenylamino)-5,8- quinolinedione; 1 and 3 microM), compounds which inhibit NO-induced stimulation of guanylate cyclase. SIN-1 produced a negative chronotropic effect in right atria; however, this action was not observed at concentrations less than 300 microM and was not antagonized by methylene blue or LY-83,583. 8-Bromo cyclic GMP produced a dose-dependent (10-3000 microM) decrease in KCl-induced tension in aortic rings. In right atria, 8-bromo cyclic GMP elicited a positive chronotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Kennedy
R H
RH
Department of Pharmacology, University of Arkansas for Medical Sciences, Little Rock 72205.
Hicks
K K
KK
Brian
J E
JE
Seifen
E
E
D000109:Acetylcholine / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006325:Heart Atria / Q000187:drug effects / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019335:Nitroarginine; D009638:Norepinephrine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D000634:Aminoquinolines; D014665:Vasodilator Agents; D019335:Nitroarginine; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C002385:linsidomine; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; D008981:Molsidomine; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D000109:Acetylcholine; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine