AUTHOR=Berg Torill 

TITLE=Angiotensin AT1 – α2C-Adrenoceptor Interaction Disturbs α2A-auto-Inhibition of Catecholamine Release in Hypertensive Rats

JOURNAL=Frontiers in Neurology

VOLUME=4

YEAR=2013

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2013.00070

DOI=10.3389/fneur.2013.00070

ISSN=1664-2295

ABSTRACT=<p>α<sub>2</sub>-Adrenoceptors lower central sympathetic output and peripheral catecholamine release, and thus may prevent sympathetic hyperactivity and hypertension. α<sub>2</sub>AR also influence vascular tension. These α<sub>2</sub>AR are malfunctioning in spontaneously hypertensive rats (SHR). Here I tested if an interaction between α<sub>2</sub>AR subtypes and the angiotensin AT1 receptor (AT<sub>1</sub>R) precipitated these disorders. Blood pressure was monitored through a femoral artery catheter and cardiac output by ascending aorta flow in anesthetized rats. Catecholamine concentrations were determined in plasma collected at the end of a 15-min tyramine-infusion. Tyramine stimulates norepinephrine release through the re-uptake transporter, thus preventing re-uptake. Presynaptic control of vesicular release is therefore reflected as differences in overflow to plasma. Previous experiments showed surgical stress to activate some secretion of epinephrine, also subjected to α<sub>2</sub>AR-auto-inhibition. Normotensive rats (WKY) and SHR were pre-treated with (1) vehicle or α<sub>2</sub>AR-antagonist (L-659,066), followed by fadolmidine (α<sub>2C&gt;B&gt;A</sub> + α<sub>1</sub>AR-agonist), ST-91 (α<sub>2non-A</sub>-selective agonist), or <italic>m</italic>-nitrobiphenyline (α<sub>2C</sub>AR-agonist + α<sub>2A+B</sub>-antagonist), or (2) AT1R-antagonist losartan, losartan + L-659,066, or losartan + clonidine. In WKY, L-659,066 alone, L-659,066 + agonist or losartan + L-659,066 increased catecholamine overflow to plasma after tyramine and eliminated the norepinephrine-induced rise in total peripheral vascular resistance (TPR). In SHR, L-659,066 + fadolmidine/ST-91/<italic>m</italic>-nitrobiphenyline and losartan + L-659,066 greatly increased, and losartan + clonidine reduced, catecholamine concentrations, and L-659,066 + ST-91, losartan + L-659,066 and losartan + clonidine eliminated the tyramine-induced rise in TPR. Separately, these drugs had no effect in SHR. In conclusion, peripheral α<sub>2C</sub>AR-stimulation or AT<sub>1</sub>R-inhibition restored failing α<sub>2A</sub>AR-mediated auto-inhibition of norepinephrine and epinephrine release and control of TPR in SHR.</p>