AUTHOR=Berg Torill 

TITLE=Altered β1-3-adrenoceptor influence on α2-adrenoceptor-mediated control of catecholamine release and vascular tension in hypertensive rats

JOURNAL=Frontiers in Physiology

VOLUME=Volume 6 - 2015

YEAR=2015

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2015.00120

DOI=10.3389/fphys.2015.00120

ISSN=1664-042X

ABSTRACT=<p>α<sub>2</sub>- and β-adrenoceptors (AR) reciprocally control catecholamine release and vascular tension. Disorders in these functions are present in spontaneously hypertensive rats (SHR). The present study tested if α<sub>2</sub>AR dysfunctions resulted from altered α<sub>2</sub>AR/βAR interaction. Blood pressure (BP) was recorded through a femoral artery catheter and cardiac output by an ascending aorta flow probe. Total peripheral vascular resistance (TPR) was calculated. Norepinephrine release was stimulated by a 15-min tyramine-infusion, which allows presynaptic release-control to be reflected as differences in overflow to plasma. Surgical stress activated some secretion of epinephrine. L-659,066 (α<sub>2</sub>AR-antagonist) enhanced norepinephrine overflow in normotensive controls (WKY) but not SHR. Nadolol (β<sub>1+2</sub>) and ICI-118551 (β<sub>2</sub>), but not atenolol (β<sub>1</sub>) or SR59230A [β<sub>(3)/1<italic>L</italic></sub>] prevented this increase. All βAR antagonists allowed L-659,066 to augment tyramine-induced norepinephrine overflow in SHR and epinephrine secretion in both strains. Inhibition of cAMP-degradation with milrinone and β<sub>3</sub>AR agonist (BRL37344) enhanced the effect of L-659,066 on release of both catecholamines in SHR and epinephrine in WKY. β<sub>1/2</sub>AR antagonists and BRL37344 opposed the L-659,066-dependent elimination of the TPR-response to tyramine in WKY. α<sub>2</sub>AR/βAR antagonists had little influence on the TPR-response in SHR. Milrinone potentiated the L-659,066-dependent reduction of the TPR-response to tyramine. Conclusions: β<sub>2</sub>AR activity was a required substrate for α<sub>2</sub>AR auto inhibition of norepinephrine release in WKY. β<sub>1+2</sub>AR opposed α<sub>2</sub>AR inhibition of norepinephrine release in SHR and epinephrine secretion in both strains. βAR-α<sub>2</sub>AR reciprocal control of vascular tension was absent in SHR. Selective agonist provoked β<sub>3</sub>AR-G<sub>i</sub> signaling and influenced the tyramine-induced TPR-response in WKY and catecholamine release in SHR.</p>