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

-Adrenoceptors contribute to hypertension in spite of the fact that -adrenoceptor agonists lower blood pressure. We aimed to differentiate between these functions and to identify differences between spontaneously hypertensive and normotensive rats. -Adrenoceptor antagonists with different subtype selectivity or the ability to cross the blood-brain barrier were used to demonstrate -adrenoceptor involvement in resting blood pressure and the response to tyramine-induced peripheral norepinephrine release. The centrally acting propranolol ( 1 2[ 3]), CGP20712A ( 1), ICI-118551 ( 2), and SR59230A ( 3), as well as peripherally restricted nadolol ( 1 2) and atenolol ( 1), were administered intravenously, separately, or in combinations. Blood pressure, cardiac output, heart rate, total peripheral vascular resistance, and plasma catecholamine concentrations were evaluated. -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 1-adrenoceptors, and peripheral 2-adrenoceptors. Tyramine induced a transient, prazosin-sensitive vascular resistance increase. Inhibition of nerve-activated, peripheral 1/3-adrenoceptors enhanced this 1-adrenoceptor–dependent vasoconstriction in normotensive but not hypertensive rats. In hypertensive rats, return to baseline was eliminated after inhibition of the central 1-adrenoceptor, epinephrine release (acute adrenalectomy), and peripheral 2/3-adrenoceptors. Adrenalectomy eliminated -adrenoceptor–mediated vasodilation in hypertensive rats, and tyramine induced a prazosin-sensitive vasoconstriction, which was inhibited by combined blockade of central 1and peripheral 2-adrenoceptors. In conclusion, nerve-activated 1and 3-adrenoceptor–mediated vasodilation was not present in hypertensive rats, whereas epinephrine-activated 2and 3-adrenoceptor–mediated vasodilation was upregulated. There was also a hypertensive, nerve-activated vasoconstrictory mechanism present in hypertensive rats, involving central 1and peripheral 2-adrenoceptors combined. (Hypertension. 2010;55:1224-1230.)