α ₂–Adrenoceptor activation may trigger the increased production of endothelium–derived nitric oxide in skeletal muscle during acute haemorrhage

Abstract

Our previous studies indicated that acute haemorrhage leads to a pronounced increase in the release of endothelium-derived nitric oxide (EDNO) graded in relation to the magnitude of the blood loss. The EDNO-induced vasodilatation, confined selectively to the arterial 'feeder' vessels, attenuates the concomitant reflex adrenergic constriction and thereby prevents deleterious reduction of blood flow. The present study aimed at investigating whether the reflex release of blood-borne catecholamines might trigger this EDNO release via activation of endothelial alpha 2-adrenoceptors. The study was performed on the sympathectomized vascular bed of cat skeletal muscle with a technique permitting quantitative recordings of resistance (tone) in consecutive vascular sections. Selection alpha 2-adrenoceptor blockade with idazoxan applied at steady state vasoconstriction after a 35% blood loss evoked an initial generalized dilator response (attributable to inhibition of post-synaptic smooth muscle alpha 2-adrenoceptors), followed by a constrictor response selectively in the arterial feeder vessels, the latter compatible with the hypothesis of reduced EDNO release by alpha 2-adrenoceptor blockade. More direct evidence for the hypothesis was obtained from studies of the vascular response to EDNO blockade (L-NAME) after haemorrhage in the presence and absence of alpha 2-adrenoceptor blockade. The constrictor response to EDNO blockade, which is a measure of the pre-existing EDNO dilator influence (EDNO production), was significantly smaller (P < 0.01) in the presence than absence of alpha 2-adrenoceptor blockade. The results indicate that blood-borne catecholamines, via activation of endothelial alpha 2-adrenoceptors, trigger the increase in the EDNO release in acute haemorrhage, implying a functionally important negative feedback in the integrated control of vascular tone in bleeding.

Selective inducible nitric oxide synthase (iNOS) inhibition attenuates remote acute lung injury in a model of ruptured abdominal aortic aneurysm1

“…The NOinduced vasodilatation, confined selectively to the arterial feeder vessels, attenuates the concomitant reflex adrenergic constriction and, thereby, prevents deleterious reduction of blood flow. Alpha 2-adrenoreceptor activation may trigger the increased production of NO in skeletal muscle after acute hemorrhagic shock [47]. Selective inhibition, however, has not been shown to be as effective in maintaining arterial tone as seen in this model.…”

Effect of acute sympathetic nervous system activation on flow-mediated dilation of brachial artery

“…The elevated circulating catecholamines may have played a role in augmenting NO release from the endothelium. ␣-Adrenergic receptors on the endothelium have been shown to facilitate the release of NO from the endothelium during hemorrhage (8), and ␤ 2 -receptor stimulation by salbutamol has been shown to mask hyperglycemia-induced endothelial dysfunction (21). It is unlikely that reaching the same peak dilation was a physiologically defined upper limit because many studies have shown greater dilation with nitroglycerin (18,35) or with greater shear stimulus as after ischemic exercise (1).…”

Impaired Endothelial Alpha-2 Adrenergic Receptor- Mediated Vascular Relaxation in the Fructose-Fed Rat

“…Evidence is now strong that NO mediates the α2-adrenergic receptor-induced relaxation (28)(29)(30)(31). These relaxations tend to be larger in the mesenteric artery of the SHR (30) and are impaired in the aorta of the SHRSP (32) but its status in the FFR has not been previously examined.…”