Role of β 1–3 -Adrenoceptors in Blood Pressure Control at Rest and During Tyramine-Induced Norepinephrine Release in Spontaneously Hypertensive Rats

Abstract

beta-Adrenoceptors contribute to hypertension in spite of the fact that beta-adrenoceptor agonists lower blood pressure. We aimed to differentiate between these functions and to identify differences between spontaneously hypertensive and normotensive rats. beta-Adrenoceptor antagonists with different subtype selectivity or the ability to cross the blood-brain barrier were used to demonstrate beta-adrenoceptor involvement in resting blood pressure and the response to tyramine-induced peripheral norepinephrine release. The centrally acting propranolol (beta(1+2[+3])), CGP20712A (beta(1)), ICI-118551 (beta(2)), and SR59230A (beta(3)), as well as peripherally restricted nadolol (beta(1+2)) and atenolol (beta(1)), were administered intravenously, separately, or in combinations. Blood pressure, cardiac output, heart rate, total peripheral vascular resistance, and plasma catecholamine concentrations were evaluated. beta-Adrenoceptor antagonists had little effect on cardiovascular baselines in normotensive rats. In hypertensive rats, antagonist-induced hypotension paralleled reductions in resistance, except for atenolol, which reduced cardiac output. The resistance reduction involved primarily neuronal catecholamine, central beta(1)-adrenoceptors, and peripheral beta(2)-adrenoceptors. Tyramine induced a transient, prazosin-sensitive vascular resistance increase. Inhibition of nerve-activated, peripheral beta(1/3)-adrenoceptors enhanced this alpha(1)-adrenoceptor-dependent vasoconstriction in normotensive but not hypertensive rats. In hypertensive rats, return to baseline was eliminated after inhibition of the central beta(1)-adrenoceptor, epinephrine release (acute adrenalectomy), and peripheral beta(2/3)-adrenoceptors. Adrenalectomy eliminated beta-adrenoceptor-mediated vasodilation in hypertensive rats, and tyramine induced a prazosin-sensitive vasoconstriction, which was inhibited by combined blockade of central beta(1)- and peripheral beta(2)-adrenoceptors. In conclusion, nerve-activated beta(1)- and beta(3)-adrenoceptor-mediated vasodilation was not present in hypertensive rats, whereas epinephrine-activated beta(2)- and beta(3)-adrenoceptor-mediated vasodilation was upregulated. There was also a hypertensive, nerve-activated vasoconstrictory mechanism present in hypertensive rats, involving central beta(1)- and peripheral beta(2)-adrenoceptors combined.