Premium
Effects of N G ‐substituted analogues of l ‐arginine on NANC relaxation of the rat anococcygeus and bovine retractor penis muscles and the bovine penile artery
Author(s) -
Liu Xiaorong,
Gillespie John S.,
Gibson Ian F.,
Martin William
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12384.x
Subject(s) - omega n methylarginine , chemistry , arginine , nitric oxide synthase , nitroarginine , nitric oxide , muscle relaxation , pharmacology , endocrinology , medicine , biochemistry , amino acid
1 The effects of two inhibitors of nitric oxide synthase, N G ‐monomethyl l ‐arginine ( l ‐NMMA) and N G ‐nitro l ‐arginine ( l ‐NOARG), were examined on non‐adrenergic non‐cholinergic (NANC) inhibitory transmission in the rat anococcygeus, bovine retractor penis (BRP) and bovine penile artery. 2 In the rat anococcygeus, l ‐NMMA (10–1000 μ m ) produced a concentration‐dependent augmentation of guanethidine (30 μ m )‐induced tone and inhibited NANC relaxation at all frequencies tested (0.1–20 Hz): the maximum inhibition obtained was 56 ± 6% ( n = 6). l ‐NOARG (0.3–30 μ m ) also augmented tone and inhibited NANC relaxation in a concentration‐dependent manner, but unlike l ‐NMMA the maximum inhibition was 100%. 3 In the BRP, l ‐NMMA (10–100 μ m ) had no effect on tone or NANC‐induced relaxation, but at 1000 μ m tone was increased and NANC relaxation inhibited by 25 ± 7% ( n = 6). l ‐NOARG (0.3–30 μ m ) produced a concentration‐dependent increase in tone and inhibition of NANC relaxation. As in the rat anococcygeus, inhibition of NANC relaxation was complete. 4 The effects of l ‐NMMA and l ‐NOARG were stereospecific since d ‐NMMA (10–1000 μ m ) and d ‐NOARG (1–1000 μ m ) had no effect on tone or NANC relaxation of the rat anococcygeus or BRP. 5 l ‐Arginine (10–300 μ m ) had no effect by itself on NANC‐induced relaxation of the rat anococcygeus or BRP. It did, however, reverse the ability of l ‐NMMA (10–1000 μ m ) to augment tone and inhibit NANC relaxation in the rat anococcygeus and BRP. The actions of low concentrations l ‐NOARG (0.3–10 μ m ) were also reversed by l ‐arginine (300 μ m ), but those of higher concentrations were not. d ‐Arginine (1000 μ m ) had no effect on the ability of l ‐NMMA or l ‐NOARG to augment tone and inhibit NANC relaxation in the anococcygeus and BRP. 6 On the bovine penile artery, both l ‐NMMA (100μ m ) and l ‐NOARG (30 μ m ) augmented the tone induced by guanethidine (30 μ m ) and 5‐hydroxytryptamine (0.2 μ m ) in an endothelium‐dependent manner. l ‐NMMA had no effect on NANC‐induced relaxation, but inhibited acetylcholine‐induced endothelium‐dependent relaxation. l ‐NOARG abolished NANC relaxation at all frequencies tested and inhibited acetylcholine‐induced relaxation. d ‐NOARG (30 μ m ) had no effect on NANC or acetylcholine‐induced relaxation. 7 The ability of l ‐NOARG to abolish NANC‐induced relaxation in the rat anococcygeus, BRP and bovine penile artery suggests that the l ‐arginine‐nitric oxide pathway mediates neurotransmission in all three tissues. The effectiveness of l ‐NMMA in blocking NANC relaxation in the rat anococcygeus but not the BRP and bovine penile artery suggests a species difference in the neuronal nitric oxide synthase. The neuronal and endothelial nitric oxide synthases in the penile artery also appear to differ.