Heterogeneity in mechanisms underlying vasodilatory responses in small arteries of the rat hepatic mesentery

Jacqueline K. Phillips, Haruyo Hickey, Caryl E. Hill

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

We have characterised nerve-mediated vasodilations in small arteries of the rat hepatic mesentery. Stimulation of sympathetic nerves (10 Hz, 10 s) produced a vasodilation which was abolished by the β-adrenoceptor antagonist, propranolol (2 x 10-6 M), but was unaffected by N(G)-nitro-L- arginine methyl ester (L-NAME, 10-5 M). Stimulation of sensory nerves produced a large vasodilation that was abolished by capsaicin (10-6 M). This vasodilation was unaffected by L-NAME (10-5 M), but significantly reduced by the calcitonin gene related peptide (CGRP) antagonist, CGRP8- 37 (10-6 M), or inhibition of adenylate cyclase (SQ22356, 2 x 10-5 M; 2',5'-dideoxyadenosine, 2 x 10-4 M). Stimulation of cholinergic nerves produced a small vasodilation which was significantly reduced by scopolamine (10-6 M). Expression of mRNA for CGRP1 receptors, muscarinic m2, m3 and m5 receptors and neurokinin1 (NK1) and NK3, receptors was detected. Perivascular nerves were immunoreactive for CGRP and substance P. No role was found for substance P, neuronal NO, ATP or adenosine in nerve-mediated responses. L-NAME (10-5 M) potentiated vasoconstrictions following sympathetic nerve stimulation. This effect was reversed by L-arginine (10-3 M) and cromakalim (10-6 M) and mimicked by glybenclamide (10-5 M), thus implicating K(ATP) channels. Vasodilation in response to sensory nerve stimulation was directly proportional to the level of preconstriction, while vasodilation in response to neurogenic or applied acetylcholine was inhibited at high levels of preconstriction. We hypothesize that, under conditions of intensive vasoconstriction, some endothelial-dependent vasodilations may be less important than vasodilations activated directly through the smooth muscle.

Original languageEnglish
Pages (from-to)159-170
Number of pages12
JournalAutonomic Neuroscience: Basic and Clinical
Volume83
Issue number3
DOIs
Publication statusPublished - 2 Oct 2000
Externally publishedYes

Keywords

  • Cholinergic
  • Cyclic AMP
  • Nitric oxide
  • Sensory
  • Sympathetic

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