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

Key points

The prevailing dogma about neurogenic regulation of vascular tone consists of major vasodilation caused by CGRP (and possibly substance P) released from sensory‐motor nerves and vasoconstriction caused by noradrenaline, ATP and NPY release from sympathetic nerves. Most studies on perivascular nerve mediated vasodilation are made in vitro. We here provide evidence that in vivo electrical perivascular nerve stimulation in rat mesenteric small arteries causes a large β1‐adrenoceptor mediated vasodilation, which contrasts with a smaller vasodilation caused by endogenous CGRP, which 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 vasodilation 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 2^nd 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 vasodilation in arteries constricted with 1 μm U46619 in the presence of 140 μm suramin and 1 μm prazosin. The vasodilation was inhibited by 1 μm tetrodotoxin and 5 μm guanethidine but not by the 1 μm of the CGRP receptor antagonist BIBN4096bs. In the presence of 0.3 μm of the Y1 receptor antagonist BIBP3226, BIBN4096bs partly inhibited the vasodilation. One μm atenolol inhibited the vasodilation while 0.1 μm of the β₂‐adrenoceptor selective antagonist ICI‐118,551 had no effect. Increasing the extracellular [K⁺] to 20 mm caused vasodilation but 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 dilation via sensory‐motor nerves but induced sympathetic β₁‐adrenoceptor mediated dilation.

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