Rat mesenteric small artery neurogenic dilatation is predominantly mediated by beta(1)-adrenoceptors in vivo

TY - JOUR

T1 - Rat mesenteric small artery neurogenic dilatation is predominantly mediated by beta(1)-adrenoceptors in vivo

AU - Sondergaard, Asger Maare

AU - Overgaard, Cathrine Bang

AU - Mazur, Aleksandra

AU - Postnov, Dmitry D.

AU - Matchkov, Vladimir V.

AU - Aalkjaer, Christian

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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 beta 1-adrenoceptor-mediated vasodilatation, which contrasts with a smaller vasodilatation caused by endogenous CGRP that is only visible after inhibition of Y1 NPY receptors. 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 mu m U46619 in the presence of 140 mu m suramin and 1 mu m prazosin. The vasodilatation was inhibited by 1 mu m tetrodotoxin and 5 mu m guanethidine, although not by the 1 mu m of the CGRP receptor antagonist BIBN4096bs. In the presence of 0.3 mu m Y1 receptor antagonist BIBP3226, BIBN4096bs partly inhibited the vasodilatation. Atenolol at a concentration 1 mu m inhibited the vasodilatation, whereas 0.1 mu m of the beta(2)-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 mu m 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 beta(1)-adrenoceptor-mediated dilatation.

AB - 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 beta 1-adrenoceptor-mediated vasodilatation, which contrasts with a smaller vasodilatation caused by endogenous CGRP that is only visible after inhibition of Y1 NPY receptors. 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 mu m U46619 in the presence of 140 mu m suramin and 1 mu m prazosin. The vasodilatation was inhibited by 1 mu m tetrodotoxin and 5 mu m guanethidine, although not by the 1 mu m of the CGRP receptor antagonist BIBN4096bs. In the presence of 0.3 mu m Y1 receptor antagonist BIBP3226, BIBN4096bs partly inhibited the vasodilatation. Atenolol at a concentration 1 mu m inhibited the vasodilatation, whereas 0.1 mu m of the beta(2)-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 mu m 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 beta(1)-adrenoceptor-mediated dilatation.

KW - Perivascular nerves

KW - in vivo

KW - beta 1-adrenoceptors

KW - calcitonin gene related peptide

KW - CGRP

KW - nerve-mediated vasodilation

KW - resistance arteries

KW - sensory-motor nerves

KW - sympathetic nerves

KW - vasodilation

U2 - 10.1113/jp277368

DO - 10.1113/jp277368

M3 - Journal article

C2 - 30693527

SN - 0022-3751

VL - 597

SP - 1819

EP - 1831

JO - The Journal of Physiology

JF - The Journal of Physiology

IS - 7

ER -