Heterogeneity in mechanisms underlying vasodilatory responses in small arteries of the rat hepatic mesentery.
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 beta-adrenoceptor antagonist, propranolol (2 x 10(-6) M), but was unaffected by NG-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 KATP 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.
Phillips
J K
JK
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, GPO Box 334, Canberra, ACT, 0200, Australia.
Hickey
H
H
Hill
C E
CE
D000067956:Adenylyl Cyclase Inhibitors; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006499:Hepatic Artery / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D007150:Immunohistochemistry; D008099:Liver / Q000098:blood supply*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism; D018042:Receptors, Neurokinin-3 / Q000235:genetics / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000067956:Adenylyl Cyclase Inhibitors; D000319:Adrenergic beta-Antagonists; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D010446:Peptide Fragments; D015221:Potassium Channels; D012333:RNA, Messenger; D018015:Receptors, Calcitonin Gene-Related Peptide; D011976:Receptors, Muscarinic; D018040:Receptors, Neurokinin-1; D018042:Receptors, Neurokinin-3; D014662:Vasoconstrictor Agents; C058636:calcitonin gene-related peptide (8-37); D011433:Propranolol; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester