Neurogenic Vascular Responses in Male Mouse Mesenteric Vascular Beds

Abstract

Rat mesenteric arteries were maintained by both adrenergic vasoconstrictor nerves and calcitonin gene–related peptide (CGRP) vasodilator nerves. However, functions of these nerves in a pathophysiological state have not fully been analyzed. The use of disease models developed genetically in mice is expected to clarify neural function of perivascular nerves. Thus, we investigated basic mouse vascular responses. Mesenteric vascular beds isolated from male C57BL/6 mouse were perfused with Krebs solution and perfusion pressure was measured. Periarterial nerve stimulation (PNS, 8 – 24 Hz) induced frequency-dependent vasoconstriction, which increased flow rate–dependently. PNS-induced vasoconstriction was abolished by tetrodotoxin (neurotoxin) and guanethidine (adrenergic neuron blocker) and blunted by prazosin (α1-adrenoceptor antagonist). Injection of norepinephrine caused vasoconstriction, which was abolished by prazosin. In preparations with active tone, PNS (1 – 8 Hz) induced frequency-dependent vasodilation, which was inhibited by tetrodotoxin, capsaicin (CGRP depletor), and CGRP8-37 (CGRP-receptor antagonist). Injections of CGRP, acetylcholine, and sodium nitroprusside induced vasodilations. Vasodilator response to CGRP was inhibited by CGRP8-37. Immunohistochemical study showed innervation of tyrosine hydroxylase- and CGRP-immunopositive fibers in mesenteric arteries and veins. These results suggest that male mouse mesenteric vascular beds are useful for studying neural regulation of mesenteric arteries, which are innervated by adrenergic and CGRPergic nerves regulating vascular tone. Keywords:: adrenergic vasoconstriction, calcitonin gene–related peptide (CGRP), CGRPergic vasodilation, mesenteric vascular bed, perivascular innervation