Differential effects of nifedipine and verapamil on non-adrenergic non-cholinergic relaxations at different levels of active tone: assessment of the contribution of nerve-derived hyperpolarizing factor.
1. The objective was to investigate a possible contribution of a nerve-derived hyperpolarizing factor to the differences between non-adrenergic non-cholinergic (NANC) nerve-mediated relaxations in different states of active tone in the rat gastric fundus. 2. NANC relaxations induced by electrical field stimulation (ES: 0.1, 0.5 and 1 Hz; 25 V; 1 ms; 10 s) in 40% contracted strips (S40) were greater when compared with those in 80% contracted strips (S80). 3. ES-induced relaxations were effectively attenuated by N(omega)-nitro-L-arginine (L-NNA; 100 microm) in S40 and S80. Percentage reduction of the responses obtained in the presence of L-NNA in S40 group was less than that of S80. 4. In S40 group, nifedipine (0.5-1 microm) and verapamil (0.5-1 microm) inhibited the responses to 0.1 and 0.5 Hz. Nifedipine (1 microm) and verapamil (0.5 microm) caused no change in the responses to ES in S80. 5. In S40, when L-NNA (100 microm) and nifedipine or verapamil, either in 1 microm concentration, were administered together, the inhibition on the electrical relaxations were more than that of each drug alone. 6. In conclusion, NANC nerve-mediated relaxations are increased when studied in an active state of 40%, and a factor, sensitive to nifedipine seems to be responsible for this distinction.
Ergün
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Department of Pharmacology, Faculty of Medicine, University of Cukurova, 01330, Balcali, Adana, Turkey.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D009412:Nerve Fibers / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019335:Nitroarginine; D014700:Verapamil; D019001:Nitric Oxide Synthase; D009543:Nifedipine