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 β1>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 β1>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 β1or2-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, β1/2AR-independent α2AR-mediated vasoconstriction was seen in WKY but not SHR, but β1/2AR-mediated vasodilation downregulated adrenergic vasoconstriction, not only in WKY but also in SHR.
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