The L-arginine/nitric oxide pathway in the rabbit urethral lamina propria.
A non-adrenergic, non-cholinergic (NANC)-mediated relaxation has been demonstrated in the female rabbit urethral lamina propria, both in response to electrical stimulation and after administration of acetylcholine. The present study was performed to investigate if these relaxations are mediated via the L-arginine/nitric oxide (NO) pathway. In the lamina propria of the female rabbit urethra, numerous NADPH diaphorase-positive, fine varicose nerve fibres were observed both around arteries, in and around smooth muscle bundles, and in arterial endothelium. Since NADPH diaphorase histochemistry may be a marker of NO synthase-containing neurons, this finding suggests the occurrence of NO synthase in this tissue. Isolated preparations of the rabbit urethral lamina propria, contracted by noradrenaline, produced frequency-dependent NANC relaxations in response to electrical field stimulation, and concentration-dependent NANC relaxations in response to acetylcholine. Electrically induced relaxations were possible to evoke even in preparations where acetylcholine-induced relaxation was poor or absent. Pretreatment with the NO synthase inhibitor, NG-nitro-L-arginine (L-NOARG) reduced the maximum relaxation obtained at 30 Hz to 12% of the control response. NG-nitro-D-arginine (D-NOARG) had no effect. The effects of L-NOARG were antagonized by the addition of L-arginine. Acetylcholine relaxed noradrenaline-precontracted strips by 36%; vasoactive intestinal polypeptide (VIP) reduced the contraction by 95%. L-NOARG, but not D-NOARG, abolished or reversed acetylcholine-induced relaxations, but failed to reduce the relaxations produced by VIP. The results demonstrate the occurrence of NADPH diaphorase-positive nerve fibres in the lamina propria of the female rabbit urethra.(ABSTRACT TRUNCATED AT 250 WORDS)
Zygmunt
P K
PK
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
Persson
K
K
Alm
P
P
Larsson
B
B
Andersson
K E
KE
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D003238:Connective Tissue / Q000737:chemistry / Q000502:physiology*; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000294:innervation / Q000502:physiology; D005260:Female; D009092:Mucous Membrane / Q000737:chemistry / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000294:innervation / Q000502:physiology; D009252:NADPH Dehydrogenase / Q000032:analysis; D009412:Nerve Fibers / Q000201:enzymology / Q000502:physiology; D009569:Nitric Oxide / Q000032:analysis / Q000502:physiology*; D019335:Nitroarginine; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D014521:Urethra / Q000737:chemistry / Q000502:physiology*
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D009252:NADPH Dehydrogenase; D000109:Acetylcholine; D009638:Norepinephrine