α2-Adrenergic receptor signalling in hypertension

Abstract

Cardiovascular regulation by the sympathetic nervous system is mediated by activation of one or more of the nine known subtypes of the adrenergic receptor family; alpha(1A)-, alpha(1B)-, alpha(1D)-, alpha(2A)-, alpha(2B)-, alpha(2C)-, beta(1)-, beta(2)- and beta(3)-ARs (adrenoceptors). The role of the alpha(2)-AR family has long been known to include presynaptic inhibition of neurotransmitter release, diminished sympathetic efferent traffic, vasodilation and vasoconstriction. This complex response is mediated by one of three subtypes which all uniquely affect blood pressure and blood flow. All three subtypes are present in the brain, kidney, heart and vasculature. However, each differentially influences blood pressure and sympathetic transmission. Activation of alpha(2A)-ARs in cardiovascular control centres of the brain lowers blood pressure and decreases plasma noradrenaline (norepinephrine), activation of peripheral alpha(2B)-ARs causes sodium retention and vasoconstriction, whereas activation of peripheral alpha(2C)-ARs causes cold-induced vasoconstriction. In addition, non-selective agonists elicit endothelium-dependent vasodilation and presynaptic inhibition of noradrenaline release. The evidence that each of these receptor subtypes uniquely participates in cardiovascular control is discussed in this review.

Vasopressors for cardiopulmonary resuscitation

“…One study in mice, using prazosin to block α1-adrenoceptor-mediated responses, estimated that between 55 and 68% of the vasopressor response to injected noradrenaline was mediated through α1-adrenoceptors (Duka et al 2000). However, this study may have been flawed, because prazosin is also known to act as an antagonist to some extent at α2B-and α2C-adrenoceptors (Kanagy 2005). There is some evidence that several pathophysiological features of cardiac arrest can increase the importance of α2-adrenoceptor-mediated arteriolar vasoconstriction.…”

“…However, α2-adrenoceptors are also present extrasynaptically, on smooth muscle cells and can contribute to vasoconstriction. The α2A subtype is probably the most important in this respect (Kanagy 2005).…”

“…Indeed, in rat aorta, treatment with a nitric oxide synthase inhibitor is required to unmask the vasoconstrictor response to α2-adrenoceptor stimulation (Kanagy 2005).…”

“…Ischaemia also causes severe damage to the endothelium (Sapienza et al 1996). Endothelial damage results in reduced endothelial vasodilator responses (Sapienza et al 1996;Melo et al 2004) and thus in patients presenting with cardiac arrest, the vasoconstrictor properties of α2-adrenoceptors may dominate over the endothelial vasodilator effects (Kanagy 2005).…”

“…Clonidine is unsuitable as it causes a paradoxical fall in blood pressure. This is due to activation of α2-adrenoceptors in the central nervous system causing a fall in blood pressure (Kanagy 2005).…”