The influence of L‐N<sup>G</sup>‐nitro‐arginine on sympathetic nerve induced contraction and noradrenaline release in the rat isolated anococcygeus muscle

Brave, Sandra R.; Bhat, Siva; Hobbs, Adrian J.; Tucker, John F.; Gibson, Alan

doi:10.1111/j.1474-8673.1993.tb00269.x

Cited by 24 publications

(15 citation statements)

References 13 publications

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“…In addition, EFS-induced contractions are enhanced by ODQ. Moreover, noradrenaline release is not affected by NO synthase inhibitors in the rabbit (unpublished observations) and rat anococcygeus muscle (18)(19)(20). The mechanisms involved in this postjunctional interaction certainly deserve further investigation.…”

Section: Discussionmentioning

confidence: 89%

Nitrergic control of peripheral sympathetic responses in the human corpus cavernosum: A comparison with other species

Cellek

Moncada

1997

Proc. Natl. Acad. Sci. U.S.A.

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Noradrenergic contractions induced by electrical field stimulation (EFS) of the rabbit anococcygeus muscle and the human and rabbit corpus cavernosum did not occur until termination of stimulation, even when EFS was applied for long periods (10 min). After treatment with a nitric oxide synthase inhibitor, a scavenger of NO, or a specific inhibitor of the soluble guanylate cyclase, EFS-induced contraction began as soon as stimulation commenced and its magnitude and duration were increased. In the presence of a cGMP-phosphodiesterase inhibitor, the lag period between the end of EFS and the onset of contraction was longer, and the response was smaller. Even when the concentration of endogenous noradrenaline was increased with cocaine, the contraction still did not occur during EFS and the lag period was unchanged, although the response was enhanced. When tissue tone was elevated, relaxation occurred during EFS followed by a contraction. After blockade of neuronal noradrenaline release with guanethidine, contractions of the tissues to increasing concentrations of exogenous noradrenaline were significantly reduced by EFS, an effect that was reversible by inhibition of NO synthase. In contrast, in the rat and mouse anococcygeus muscles contraction began immediately with EFS, and nitrergic stimulation by EFS did not affect the responses elicited by high concentrations of exogenous noradrenaline. These results suggest that the human and rabbit genitourinary organs have a powerful nitrergic innervation that does not merely modulate, but actually controls, the sympathetic responses. Our observations may increase understanding of the balance between nitrergic and sympathetic systems in humans, disruption of which may contribute to certain pathological conditions. The excitatory innervation of the anococcygeus muscle (1) and corpus cavernosum (2) has been known for many years to be noradrenergic. It was later found that blockade of the sympathetic nerves and elevation of tone in the tissues revealed an inhibitory, relaxant response, the mediator of which could not be identified at that time (3, 4). This relaxant response, and many similar responses in the genitourinary system, gut, bronchi, and blood vessels, was attributed to nonadrenergic, noncholinergic (NANC) innervation in the autonomic nervous system (for review, see ref. 5).The discovery in the 1980s of the biological actions of nitric oxide (6, 7) suggested that this might be the inhibitory mediator released from NANC nerves (8). This has now been widely accepted because relaxations induced by stimulation of NANC nerves are prevented by inhibitors of NO synthase, by a scavenger of NO, oxyhemoglobin (5), and by a specific inhibitor of the soluble guanylate cyclase (9). Moreover, calcium͞calmodulin-dependent constitutive NO synthase has been identified in NANC-innervated tissues (5), and NO has been shown to be released during nerve stimulation (10,

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Section: Discussionmentioning

confidence: 89%

Nitrergic control of peripheral sympathetic responses in the human corpus cavernosum: A comparison with other species

Cellek

Moncada

1997

Proc. Natl. Acad. Sci. U.S.A.

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“…This may be due to different chemical coding for different organs. It has also been reported that NO could have an inhibitory counteracting postjunctional effect on noradrenergic transmission (Toda and Okamura 1992;Brave et al 1993;Rand and Li 1993). The mechanism and significance of the cotransmission of NO, acetylcoline and noradrenaline in the pancreatic neurons needs to be investigated.…”

Section: Discussionmentioning

confidence: 95%

Colocalization of ChAT, DβH and NADPH-d in the pancreatic neurons of the newborn guinea pig

Liu

Tay

Leong

et al. 1998

Cell and Tissue Research

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Choline acetyltransferase (ChAT) as a rate-limiting enzyme in the biosynthetic pathway of acetylcholine is thought to be present in all cholinergic neurons. However, its immunoreactivity has not been successfully applied to the study of cholinergic neurons in the pancreas. In a previous study in the pancreas of newborn guinea pig we reported the colocalization of nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d), a marker for nitric oxide synthase (NOS) with various neuropeptides as well as dopamine-beta-hydroxylase (DbetaH), the enzyme responsible for converting dopamine to noradrenaline. Whether NADPH-d is colocalized with ChAT in the pancreatic neurons is not known. Also it would be interesting to find out whether noradrenaline and acetylcholine could be colocalized in the same pancreatic neurons. In the present study, a method for triple labelling of ChAT, DbetaH and NADPH-d was used to answer the above questions. Colocalization of ChAT, DbetaH and NADPH-d was constantly demonstrated in the same neurons in the same sections. It is concluded that some of the pancreatic neurons may utilize more than one neurotransmitter such as nitric oxide (NO), acetylcholine and noradrenaline to achieve their function. The possible cotransmission of acetylcholine and noradrenaline was extremely intriguing, and its mechanism and significance needs to be further investigated.

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“…After the addition of phenylephrine to isolated arteries, the rate of cyclic GMP formation increased 2–3‐fold in comparison to the basal synthesis (Plane et al ., 1996). It is unlikely that phenylephrine is causing the formation of cyclic GMP via a pathway confined to the smooth muscle cells or by acting via the release of NO from non‐adrenergic, non‐cholinergic nerves (Brave et al ., 1993), since the effect of L ‐NAME was abolished after removing the endothelium. Similarly, the significant augmentation of contraction to phenylephrine obtained in the presence of the inhibitors of Ca 2+ activated K + channels is also consistent with an activation of the endothelium.…”

Section: Discussionmentioning

confidence: 99%

An indirect influence of phenylephrine on the release of endothelium‐derived vasodilators in rat small mesenteric artery

Dora

Hinton

Walker

et al. 2000

British J Pharmacology

125

117

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1 The possibility that stimulation of smooth muscle a 1 -adrenoceptors modulates contraction via the endothelium was examined in rat small mesenteric arteries. 2 N o -nitro-L-arginine methyl ester, (L-NAME, 100 mM to inhibit NO synthase) increased contraction to single concentrations of phenylephrine (1 ± 3 mM) by approximately 2 fold (from a control level of 14.2+3.0 to 34.1+4.2% of the maximum contraction of the artery, n=20). The action of L-NAME was abolished by disrupting the endothelium.3 The subsequent addition of apamin (to inhibit small conductance Ca 2+ -activated K + channels, 50 nM) further augmented phenylephrine contractions, in an endothelium-dependent manner, to more than 3 fold above control (50.4+5.3% of the maximum contraction, n=11). 4 Charybdotoxin (non-selective inhibitor of large conductance Ca 2+ -activated K + channels, BK Ca , 50 nM) plus L-NAME augmented the level of phenylephrine contraction to 4 ± 5-fold above control (64.1+3.1%, n=5), but this e ect was independent of the endothelium. The potentiation of contraction by charybdotoxin could be mimicked with the selective BK Ca inhibitor, iberiotoxin,. 5 Apamin together with L-NAME and charybdotoxin further signi®cantly increased the phenylephrine contraction by 5 ± 6-fold, to 79.9+3.5% of the maximum contraction of the artery (n=13). 6 Phenylephrine failed directly to increase the intracellular Ca 2+ concentration in endothelial cells freshly isolated from the small mesenteric artery. 7 Stimulation of smooth muscle a 1 -adrenoceptors in the mesenteric artery induces contraction that is markedly suppressed by the endothelium. The attenuation of contraction appears to re¯ect both the release of NO from the endothelium and the e ux of K + from both endothelial and smooth muscle cells. This suggests that the release of NO and endothelium-derived hyperpolarizing factor can be evoked indirectly by agents which act only on the smooth muscle cells.

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The influence of L‐N^G‐nitro‐arginine on sympathetic nerve induced contraction and noradrenaline release in the rat isolated anococcygeus muscle

Cited by 24 publications

References 13 publications

Nitrergic control of peripheral sympathetic responses in the human corpus cavernosum: A comparison with other species

Nitrergic control of peripheral sympathetic responses in the human corpus cavernosum: A comparison with other species

Colocalization of ChAT, DβH and NADPH-d in the pancreatic neurons of the newborn guinea pig

An indirect influence of phenylephrine on the release of endothelium‐derived vasodilators in rat small mesenteric artery

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The influence of L‐NG‐nitro‐arginine on sympathetic nerve induced contraction and noradrenaline release in the rat isolated anococcygeus muscle

Cited by 24 publications

References 13 publications

Nitrergic control of peripheral sympathetic responses in the human corpus cavernosum: A comparison with other species

Nitrergic control of peripheral sympathetic responses in the human corpus cavernosum: A comparison with other species

Colocalization of ChAT, DβH and NADPH-d in the pancreatic neurons of the newborn guinea pig

An indirect influence of phenylephrine on the release of endothelium‐derived vasodilators in rat small mesenteric artery

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The influence of L‐N^G‐nitro‐arginine on sympathetic nerve induced contraction and noradrenaline release in the rat isolated anococcygeus muscle