Affiliation:
1. From the Department of Physiology (T.B., B.W.P.), Institute for Basic Medical Sciences, University of Oslo, Oslo, Norway; Department of Physiology (J.J.), National Institute of Occupational Health, Oslo, Norway.
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
22 articles.
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