α2-adrenoreceptor constraint of catecholamine release and blood pressure is enhanced in female spontaneously hypertensive rats

Abstract

α2-adrenoceptors (α2AR) lower central sympathetic output and peripheral catecholamine release, and may therefore prevent sympathetic hyperactivity and hypertension. The α2AR are dysfunctional in male spontaneously hypertensive rats (SHR). Premenopausal females are less hypertensive than males. The purpose of this study was to test if this difference could be explained by functional α2AR in the female SHR. A 15-min tyramine-infusion was used to stimulate norepinephrine release through the re-uptake transporter, consequently preventing re-uptake. Presynaptic control of vesicular release will therefore be reflected as differences in overflow to plasma. The surgical trauma activates secretion of epinephrine, also subjected to α2AR auto-inhibition. Blood pressure was monitored through a femoral artery catheter and cardiac output by ascending aorta flow in 12-14 weeks-old (early hypertension) SHR and normotensive rats (WKY). Total peripheral vascular resistance (TPR) was calculated. Female SHR, unlike male, were close to normotensive. Pre-treatment with none-selective (clonidine) or non-A-selective (ST-91) α2AR agonist reduced, and none-selective α2AR antagonist (L-659,066) increased tyramine-induced norepinephrine overflow in female WKY and SHR. L-659,066 also increased secretion of epinephrine. The L-659,066-induced increase in catecholamine release was further enhanced by additional pre-treatment with ST-91 or angiotensin AT1 receptor antagonist (losartan) in SHR only. L-659,066 eliminated the tyramine-induced rise in TPR in both strains in female rats. Conclusion: α2AR-mediated control of catecholamine release and vascular tension was therefore functional in female SHR, unlike that previously observed in male SHR. Functional α2AR is likely to have a protective function and may explain the lack of hypertension in the young female SHR.