β-Adrenergic receptors and nitric oxide generation in the cardiovascular system

Abstract

Nitric oxide plays a crucial role in cardiovascular homeostasis, with important vasodilatory, anti-thrombotic and anti-atherogenic properties. Beta-adrenergic receptors (betaARs), present on a wide variety of cardiovascular cells, including vascular endothelial cells, platelets, cardiac myocytes and leukocytes, have long been established as key players in maintaining cardiovascular homeostatic control. During the last few years a wealth of evidence has emerged which directly links stimulation of these cardiovascular betaARs to nitric oxide (NO) generation, suggesting a new and important mechanism of adrenergic control of cardiovascular function. This review explores the cardiovascular cell systems in which this coupling of betaARs and NO occurs, the intracellular signalling and regulatory mechanisms involved and the abnormalities in betaAR-NO oxide coupling found in cardiovascular disease states.

Implications of a Vasodilatory Human Monoclonal Autoantibody in Postural Hypotension

“…The functional activity of C5F2 was consistent with that of serum IgG polyclonal autoantibodies from the patient and of serum anti-␤ 2 AR autoantibodies harbored in a subgroup of postural hypotension patients (21,22). ␤ 2 AR-mediated vasodilatation in resistance arteries involves two different mechanisms: direct vasodilatation via activation of cAMP/PKA-mediated dephosphorylation of the smooth muscle myosin (37) and endothelial nitric oxidemediated vasodilatation (38). The finding that ␤ 2 AR-activating autoantibodies intrinsically possess the capability to induce significant systemic arteriolar vasodilatation suggests that these autoantibodies may contribute to postural hypotension by altering the normal autonomic response to upright posture.…”

Inhibition of vascular smooth muscle G protein-coupled receptor kinase 2 enhances α1D-adrenergic receptor constriction

“…Another reason why VSM GRK2 inhibition may not have been sufficient to rescue hypertension could be because vascular endothelial cells also express ␤ARs and their stimulation leads to nitric oxide release and subsequent vasodilation (39). Similar to VSM, the endothelial ␤AR response is likely also desensitized in high BP.…”

Antioxidants but not Doxycycline Treatments Restore Depressed Beta-Adrenergic Responses of the Heart in Diabetic Rats

“…The current hypothesis and consequence of related experimental data on alterations in the myocardial bAR system of experimental diabetic rats was supported further with the data, which demonstrated a reversing capability of these altered inotropic responses as well as reduction in the number of b-adrenoceptors with in vivo antioxidant treatment of the diabetic rats [38][39][40]. One of the important finding in the present radioligand binding study was that the proportion of bAR binding agonist with high affinity, determined by competitive binding with ISO, was not changed in diabetic myocardium, which was similar to the previously published data on experimental diabetes and a heart failure model with selenium-deficient rats [18,41].…”