AUTHOR=Berg Torill 

TITLE=β1-Blockers Lower Norepinephrine Release by Inhibiting Presynaptic, Facilitating β1-Adrenoceptors in Normotensive and Hypertensive Rats

JOURNAL=Frontiers in Neurology

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2014.00051

DOI=10.3389/fneur.2014.00051

ISSN=1664-2295

ABSTRACT=<p>Peripheral norepinephrine release is facilitated by presynaptic β-adrenoceptors, believed to involve the β<sub>2</sub>-subtype exclusively. However, β<sub>1</sub>-selective blockers are the most commonly used β-blockers in hypertension. Here the author tested the hypothesis that β<sub>1</sub>AR may function as presynaptic, release-facilitating auto-receptors. Since β<sub>1</sub>AR-blockers are injected during myocardial infarction, their influence on the cardiovascular response to acute norepinephrine release was also studied. By a newly established method, using tyramine-stimulated release through the norepinephrine transporter (NET), presynaptic control of catecholamine release was studied in normotensive and spontaneously hypertensive rats. β<sub>1</sub>AR-selective antagonists (CGP20712A, atenolol, metoprolol) reduced norepinephrine overflow to plasma equally efficient as β<sub>2</sub>AR-selective (ICI-118551) and β<sub>1+2</sub>AR (nadolol) antagonists in both strains. Neither antagonist lowered epinephrine secretion. Atenolol, which does not cross the blood–brain barrier, reduced norepinephrine overflow after adrenalectomy (AdrX), AdrX + ganglion blockade, losartan, or nephrectomy. Atenolol and metoprolol reduced resting cardiac work load. During tyramine-stimulated norepinephrine release, they had little effect on work load, and increased the transient rise in total peripheral vascular resistance, particularly atenolol when combined with losartan. In conclusion, β<sub>1</sub>AR, like β<sub>2</sub>AR, stimulated norepinephrine but not epinephrine release, independent of adrenal catecholamines, ganglion transmission, or renal renin release/angiotensin AT1 receptor activation. β<sub>1</sub>AR therefore functioned as a peripheral, presynaptic, facilitating auto-receptor. Like tyramine, hypoxia may induce NET-mediated release. Augmented tyramine-induced vasoconstriction, as observed after injection of β<sub>1</sub>AR-blocker, particularly atenolol combined with losartan, may hamper organ perfusion, and may have clinical relevance in hypoxic conditions such as myocardial infarction.</p>