Involvement of sensory nerves in vasodilator responses to acetylcholine and potassium ions in rat hepatic artery.
In the presence of ouabain (1 mM), acetylcholine and KCl (5 mM) evoked endothelium-independent relaxations in rat hepatic arteries. Treatment with capsaicin (10 microM), scopolamine (1 microM) or CGRP(8 - 37) (3 microM) prevented these relaxations. Acetylcholine-induced relaxations in intact arterial segments in the presence of indomethacin (10 microM) and N(G)-nitro-L-arginine (0.3 mM) were only partially inhibited by ouabain plus BaCl(2) (30 microM). However, ouabain plus BaCl(2) almost abolished such relaxations in capsaicin-pre-treated preparations. In arteries without endothelium, the neurosecretagogue alpha-latrotoxin (1 nM) induced complete relaxations, which were abolished by CGRP(8 - 37) or pre-treatment with capsaicin. alpha-Latrotoxin also induced a smooth muscle hyperpolarization (12+/-2 mV), which was abolished by CGRP(8 - 37). The ability of ouabain to disclose a CGRP-mediated neurogenic relaxation must be considered when this agent is used as a pharmacological tool. The results further suggest that CGRP is a nerve-derived hyperpolarizing factor in the rat hepatic artery.
Högestätt
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ED
Department of Clinical Pharmacology, Institute of Laboratory Medicine, Lund University, SE-221 85 Lund, Sweden. Edward.Hogestatt@klinfarm.lu.se
Johansson
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R
Andersson
D A
DA
Zygmunt
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PM
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001685:Biological Factors / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006499:Hepatic Artery / Q000187:drug effects* / Q000294:innervation; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D001685:Biological Factors; D002316:Cardiotonic Agents; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D010042:Ouabain; D011189:Potassium Chloride; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine