Article date: September 1991
By: Xiaorong Liu, John S. Gillespie, Ian F. Gibson, William Martin, in Volume 104, Issue 1, pages 53-58
The effects of two inhibitors of nitric oxide synthase, NG‐monomethyl l‐arginine (l‐NMMA) and NG‐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.
In the rat anococcygeus, l‐NMMA (10–1000 μm) produced a concentration‐dependent augmentation of guanethidine (30 μm)‐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 μm) also augmented tone and inhibited NANC relaxation in a concentration‐dependent manner, but unlike l‐NMMA the maximum inhibition was 100%.
In the BRP, l‐NMMA (10–100 μm) had no effect on tone or NANC‐induced relaxation, but at 1000 μm tone was increased and NANC relaxation inhibited by 25 ± 7% (n = 6). l‐NOARG (0.3–30 μm) produced a concentration‐dependent increase in tone and inhibition of NANC relaxation. As in the rat anococcygeus, inhibition of NANC relaxation was complete.
The effects of l‐NMMA and l‐NOARG were stereospecific since d‐NMMA (10–1000 μm) and d‐NOARG (1–1000 μm) had no effect on tone or NANC relaxation of the rat anococcygeus or BRP.
l‐Arginine (10–300 μm) 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 μm) to augment tone and inhibit NANC relaxation in the rat anococcygeus and BRP. The actions of low concentrations l‐NOARG (0.3–10 μm) were also reversed by l‐arginine (300 μm), but those of higher concentrations were not. d‐Arginine (1000 μm) had no effect on the ability of l‐NMMA or l‐NOARG to augment tone and inhibit NANC relaxation in the anococcygeus and BRP.
On the bovine penile artery, both l‐NMMA (100μm) and l‐NOARG (30 μm) augmented the tone induced by guanethidine (30 μm) and 5‐hydroxytryptamine (0.2 μm) 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 μm) had no effect on NANC or acetylcholine‐induced relaxation.
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.
The effects of two inhibitors of nitric oxide synthase, NG‐monomethyl l‐arginine (l‐NMMA) and NG‐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.
In the rat anococcygeus, l‐NMMA (10–1000 μm) produced a concentration‐dependent augmentation of guanethidine (30 μm)‐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 μm) also augmented tone and inhibited NANC relaxation in a concentration‐dependent manner, but unlike l‐NMMA the maximum inhibition was 100%.
In the BRP, l‐NMMA (10–100 μm) had no effect on tone or NANC‐induced relaxation, but at 1000 μm tone was increased and NANC relaxation inhibited by 25 ± 7% (n = 6). l‐NOARG (0.3–30 μm) produced a concentration‐dependent increase in tone and inhibition of NANC relaxation. As in the rat anococcygeus, inhibition of NANC relaxation was complete.
The effects of l‐NMMA and l‐NOARG were stereospecific since d‐NMMA (10–1000 μm) and d‐NOARG (1–1000 μm) had no effect on tone or NANC relaxation of the rat anococcygeus or BRP.
l‐Arginine (10–300 μm) 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 μm) to augment tone and inhibit NANC relaxation in the rat anococcygeus and BRP. The actions of low concentrations l‐NOARG (0.3–10 μm) were also reversed by l‐arginine (300 μm), but those of higher concentrations were not. d‐Arginine (1000 μm) had no effect on the ability of l‐NMMA or l‐NOARG to augment tone and inhibit NANC relaxation in the anococcygeus and BRP.
On the bovine penile artery, both l‐NMMA (100μm) and l‐NOARG (30 μm) augmented the tone induced by guanethidine (30 μm) and 5‐hydroxytryptamine (0.2 μm) 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 μm) had no effect on NANC or acetylcholine‐induced relaxation.
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.
DOI: 10.1111/j.1476-5381.1991.tb12384.x
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