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

Abstract

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.

Hypoxic Conditions Promote Rhythmic Contractile Oscillations Mediated by Voltage-Gated Sodium Channels Activation in Human Arteries

“…However, the oscillatory activity was not affected either by prazosin or by guanethidine, an inhibitor of vesicular release of norepinephrine/ATP. This eliminates the hypothesis of a neurogenic origin [ 33 ] and, therefore, supports the idea that Na v channels of the SMCs compartment are involved in the genesis and maintenance of vasomotion.…”

Dynein Coordinates β2-Adrenoceptor-Mediated Relaxation in Normotensive and Hypertensive Rat Mesenteric Arteries

“…10 Evidence suggests that β1-adrenoceptors predominate, particularly in the rat mesenteric vasculature. 7–9,42,43 Using selective β1- and β2-adrenoceptor antagonists, our data support a predominating role of β1-adrenoceptors underling the isoprenaline-mediated vasorelaxations in control rat mesenteric arteries. However, we found that increased β2-adrenoceptor activity was responsible for the ciliobrevin D-enhanced isoprenaline relaxation, since ICI 118 551 abolished the effect of ciliobrevin D on the isoprenaline relaxation.…”

Effects of Calcitonin-Gene-Related-Peptide on Auditory Nerve Activity

“…Studies in awake animals would have the added benefit of precluding the possibility that ketamine anesthesia may attenuate responses to CGRP. The effects of CGRP are commonly measured in ketamine-anesthetized animals ( Radziszewski et al, 2003 ; Sakamoto et al, 2014 ; Sakamoto et al, 2017 ; Søndergaard et al, 2019 ). However, intra-venous ketamine attenuated CGRP-induced vasodilation of the dural artery in rats ( Chan et al, 2010 ).…”