Nitric oxide-dependent and -independent neurogenic relaxation of isolated dog urethra.
In the presence of adrenergic and cholinergic blocking agents, transmural electrical stimulation evoked a relaxation in isolated dog urethra precontracted with histamine. The response was abolished by tetrodotoxin, indicating its neurogenic origin. The non-adrenergic and non-cholinergic relaxation developed rapidly and was transient at low stimulation frequencies (< or = 1 Hz). However, at higher frequencies (> or = 5 Hz) the recovery phase of the relaxation became slow and often showed a notch, suggesting the presence of transient and slow components. NG-Monomethyl-L-arginine, a nitric oxide synthase inhibitor, inhibited the transient relaxation but did not affect the relaxation evoked at high stimulation frequencies. NG-Nitro-L-arginine, a more potent nitric oxide synthase inhibitor, abolished the transient relaxation produced at low stimulation frequencies and markedly attenuated the transient component at high frequencies. However, NG-nitro-L-arginine did not affect the slow component. The inhibition by NG-monomethyl-L-arginine and NG-nitro-L-arginine was reversed by the addition of L- but not D-arginine. Exogenously applied vasoactive intestinal polypeptide (VIP) produced a slowly developing relaxation. The slow relaxation induced by transmural electrical stimulation and VIP was not affected by [4-Cl-D-Phe6,Leu17]VIP, a reportedly competitive VIP antagonist. NG-Nitro-L-arginine did not affect the relaxation induced by VIP and sodium nitroprusside. These results suggest that the non-adrenergic and non-cholinergic relaxation induced by transmural electrical stimulation is composed of nitric oxide-dependent and -independent components in the isolated dog urethra.
Hashimoto
S
S
Department of Pharmacology, Fukui Medical School, Japan.
Kigoshi
S
S
Muramatsu
I
I
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D004558:Electric Stimulation; D004566:Electrodes; D005260:Female; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D014521:Urethra / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives / Q000494:pharmacology; D019323:omega-N-Methylarginine
C048507:vasoactive intestinal peptide, 4-chloro-Phe(6)-Leu(17)-; D009599:Nitroprusside; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D006632:Histamine; D001120:Arginine