Neurogenic Vascular Responses in Male Mouse Mesenteric Vascular Beds

Hiroki Fujiwara; Narumi Hashikawa-Hobara; Yoshihiro Wake; Shingo Takatori; Mitsuhiro Goda; Hiroshi Higuchi; Yoshito Zamami; Panot Tangsucharit; Hiromu Kawasaki

doi:10.1254/jphs.12014FP

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Neurogenic Vascular Responses in Male Mouse Mesenteric Vascular Beds

Hiroki Fujiwara, Narumi Hashikawa-Hobara, Yoshihiro Wake, Shingo Takatori, Mitsuhiro Goda, Hiroshi Higuchi, Yoshito Zamami, Panot Tangsucharit, Hiromu Kawasaki

Author information

Hiroki Fujiwara
Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan
Narumi Hashikawa-Hobara
Department of Life Science, Okayama University of Science, Japan
Yoshihiro Wake
Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan
Shingo Takatori
Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan
Mitsuhiro Goda
Division of Pharmacology, Molecular and Cellular Medicine, Niigata University Graduate School of Medical and Dental Sciences, Japan
Hiroshi Higuchi
Division of Pharmacology, Molecular and Cellular Medicine, Niigata University Graduate School of Medical and Dental Sciences, Japan
Yoshito Zamami
Department of Molecular Design for Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan
Panot Tangsucharit
Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan
Hiromu Kawasaki
Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan

Keywords: adrenergic vasoconstriction, calcitonin gene–related peptide (CGRP), CGRPergic vasodilation, mesenteric vascular bed, perivascular innervation

JOURNAL FREE ACCESS

2012 Volume 119 Issue 3 Pages 260-270

DOI https://doi.org/10.1254/jphs.12014FP

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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.

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