Vladimir Matchkov

Rat mesenteric small artery neurogenic dilatation is predominantly mediated by β1 -adrenoceptors in vivo

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

KEY POINTS: The prevailing dogma about neurogenic regulation of vascular tone consists of major vasodilatation caused by CGRP (and possibly substance P) released from sensory-motor nerves and vasoconstriction caused by noradrenaline, ATP and neuropeptode Y release from sympathetic nerves. Most studies on perivascular nerve-mediated vasodilatation are made in vitro. In the present study, we provide evidence indicating that in vivo electrical perivascular nerve stimulation in rat mesenteric small arteries causes a large β1-adrenoceptor-mediated vasodilatation, which contrasts with a smaller vasodilatation caused by endogenous CGRP that is only visible after inhibition of Y1 NPY receptors.

ABSTRACT: Mesenteric arteries are densely innervated and the nerves are important regulators of vascular tone and hence blood pressure and blood flow. Perivascular sensory-motor nerves have been shown to cause vasodilatation in vitro. However, less is known about their function in vivo. Male Wistar rats (10-12 weeks old; n = 72) were anaesthetized with ketamine (3 mg kg-1 ) and xylazine (0.75 mg kg-1 ) or pentobarbital (60 mg kg-1 ). After a laparotomy, a section of second-order mesenteric artery was visualized in an organ bath after minimal removal of perivascular adipose tissue. The effects of electrical field stimulation (EFS) and drugs on artery diameter and blood flow were recorded with intravital microscopy and laser speckle imaging. EFS caused vasodilatation in arteries constricted with 1 μm U46619 in the presence of 140 μm suramin and 1 μm prazosin. The vasodilatation was inhibited by 1 μm tetrodotoxin and 5 μm guanethidine, although not by the 1 μm of the CGRP receptor antagonist BIBN4096bs. In the presence of 0.3 μm Y1 receptor antagonist BIBP3226, BIBN4096bs partly inhibited the vasodilatation. Atenolol at a concentration 1 μm inhibited the vasodilatation, whereas 0.1 μm of the β2 -adrenoceptor selective antagonist ICI-118,551 had no effect. Increasing the extracellular [K+ ] to 20 mm caused vasodilatation but was converted to vasoconstriction in the presence of 1 μm BIBN4096bs, and constriction to 30 mm potassium was potentiated by BIBN4096bs. Atenolol but not BIBN4096bs increased contraction to EFS in the absence of suramin and prazosin. In mesenteric small arteries of anaesthetized rats, EFS failed to stimulate major dilatation via sensory-motor nerves but induced sympathetic β1 -adrenoceptor-mediated dilatation.

Original languageEnglish
JournalThe Journal of Physiology
Volume597
Issue7
Pages (from-to)1819-1831
Number of pages13
ISSN0022-3751
DOIs
Publication statusPublished - Apr 2019

    Research areas

  • CGRP, Perivascular nerves, calcitonin gene related peptide, in vivo, nerve-mediated vasodilation, resistance arteries, sensory-motor nerves, sympathetic nerves, vasodilation, ß1-adrenoceptors

See relations at Aarhus University Citationformats

ID: 148001052