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

Abstract

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