Differences in the nitric oxide/soluble guanylyl cyclase signalling pathway in the myocardium of neonatal and adult rats.
The effects of a nitric oxide-donor, S-nitroso-N-acetylpenicillamine, and a direct activator of soluble guanylyl cyclase, 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), on force of contraction (F(c)) and L-type Ca(2+) currents (I(Ca(L))) were investigated in myocardial preparations from neonatal and adult rats. Since hearts from adult and neonatal animals contained 160 and 47 mg/100 g wet weight myoglobin, respectively, its possible interaction with both drugs was also investigated. Both S-nitroso-N-acetylpenicillamine (100 microM) and YC-1 (30 microM) were ineffective in myocardial preparations from adult rats but reduced the magnitude of I(Ca(L)) and F(c) in preparations from neonatal rats. The latter effects were antagonised by 1H-[1,2, 4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 50 microM) and attenuated by myoglobin (30-300 microM), which also attenuated the effects of both drugs on pre-contracted aortic rings. The differential effects of S-nitroso-N-acetylpenicillamine and YC-1 in the myocardium from adult and neonatal rats may result from developmental changes in the content of myoglobin and/or in the NO/soluble guanylyl cyclase signal pathway.
Vulcu
S D
SD
Department of Pharmacology, Johannes Gutenberg University, 55101, Mainz, Germany.
Wegener
J W
JW
Nawrath
H
H
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D020746:Calcium Channels, L-Type / Q000187:drug effects; D006152:Cyclic GMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000502:physiology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009211:Myoglobin / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D020746:Calcium Channels, L-Type; D009211:Myoglobin; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D010396:Penicillamine; D006152:Cyclic GMP