β- and α₂-Adrenoceptor Control of Vascular Tension and Catecholamine Release in Female Normotensive and Spontaneously...

As in humans, young, female, spontaneously hypertensive rats (SHR) have a lower blood pressure than male SHR. In male, normotensive rats (WKY), α₂- and β₁₊₂-adrenoceptors (AR) reciprocally controlled catecholamine release and vascular smooth muscle tension. This interaction was malfunctioning in male SHR. The present study analyzed if a favorable shift in the α₂/β₁₊₂AR interaction may represent an antihypertensive protection in females. Female SHR (early hypertension, 12-14 weeks) and age-matched WKY were infused with tyramine (15 min) to stimulate norepinephrine (NE) release through the reuptake transporter, consequently preventing reuptake. Presynaptic control of vesicular release was therefore reflected as differences in overflow to plasma. The released NE increased total peripheral vascular resistance (TPR). The results showed that β_1>2AR facilitated tyramine-stimulated NE release in both strains, also in the presence of α₂AR-antagonist (L-659,066). βAR-antagonist (atenolol-β₁, ICI-118551-β₂, nadolol-β₁₊₂) had no effect on the increased secretion of epinephrine after L-659,066 in WKY, but β_1>2AR-antagonist augmented the L-659,066-induced increase in the secretion of epinephrine in SHR. Nadolol increased the TPR response to tyramine with a greater effect in WKY than SHR, whereas β_1or2-selective antagonists did not. One βAR-subtype may therefore substitute for the other. When both β₁₊₂AR were blocked, α₂AR-antagonist still reduced the TPR response in WKY but not SHR. Thus, α₂/β₁₊₂AR reciprocally controlled catecholamine release, with a particular negative β₁AR-influence on α₂AR-auto-inhibition of epinephrine secretion in SHR. Moreover, in these female rats, β_1/2AR-independent α₂AR-mediated vasoconstriction was seen in WKY but not SHR, but β_1/2AR-mediated vasodilation downregulated adrenergic vasoconstriction, not only in WKY but also in SHR.