Evidence that both nitric oxide (NO) and a non-NO hyperpolarizing factor elicit NANC nerve-mediated relaxation in the rat isolated anocococcygeus.
1. Responses to electrical field stimulation (EFS; 0.5-10 Hz, 0.2 ms duration, supramaximal voltage for 20 s) of non-adrenergic, non-cholinergic, (NANC) nerves were obtained in preparations of rat anococcygeus pre-contracted with titrated concentrations of phenylephrine (0.1-1 microM) to approximately 40% of their maximum contraction to phenylephrine (Fmax) regardless of drug treatment. 2. With this set level of active force, NANC nerve stimulation resulted in relaxations that were maximal (peak relaxation) at 0.5-1 Hz, abolished by tetrodotoxin (1 microM) but only minimally blocked by the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine, (L-NOARG; 100 microM). Furthermore, the nitric oxide (NO) scavenger, oxyhaemoglobin (HbO; 30 microM) gave no further block alone or in combination with L-NOARG (100 microM). By comparison, in preparations contracted with phenylephrine to approximately 70% Fmax, relaxations to NANC nerve stimulation were markedly reduced or abolished by combined treatment with L-NOARG (100 microM) and HbO (30 microM). 3. Nifedipine (0.3 microM) significantly inhibited NANC nerve-mediated relaxations, which became frequency-dependent and abolished those resistant to L-NOARG (100 microM) and HbO (30 microM). 4. These data suggest that a non-NO, hyperpolarizing factor and NO both contribute to NANC nerve-mediated inhibitory responses in the rat anococcygeus. However, responses to the non-NO factor were observed only in preparations contracted sub-maximally by a nifedipine-sensitive mechanism.
Selemidis
S
S
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Cocks
T M
TM
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D009126:Muscle Relaxation; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D009543:Nifedipine