RESERPINE INDUCES VASCULAR ALPHA-2-ADRENERGIC SUPERSENSITIVITY AND PLATELET ALPHA-2-ADRENOCEPTOR UP-REGULATION IN DOG

The aim of the present study was to investigate the influence of catecholamine levels on the regulation of α2-adenoceptor sensitivity in dogs. 2. Blood pressure and heart rate values at rest, plasma catecholamine levels, platelet and adipocyte α2-adrenoceptors as well as the α2-mediated cardiovascular responses to clonidine (10 μg kg-1 i.v., after α1, β-adrenoceptor plus muscarinic blockade) or noradrenaline (0.5, 1, 2 and 4 μg kg-1 i.v. after α1- and β-adrenoceptor blockade) were measured before and after reserpine treatment (0.1 mg kg-1 day s.c. over 15 days). 3. Reserpine induced a significant decrease in resting systolic and diastolic blood pressures (213 ± 2/87 ± 6 mmHg before vs 158 ± 5/59 ± 3 mmHg after treatment) as well as in heart rate (91 ± 2 beats min-1 before vs 76 ± 3 beats min-1 after treatment). 4. A 5 min tilt test performance under chloralose anesthesia, failed to modify blood pressure before treatment whereas it induced a significant fall in the same animals after the 15 day treatment. Plasma levels of noradrenaline significantly decreased (262 ± 58 vs 66 ± 31 pg ml-1) whereas plasma adrenaline levels were unchanged. 5. The α2-mediated pressor response to noradrenaline were significantly increased after reserpine. Clonidine induced a marked pressor effect (+72 and +45% in systolic and diastolic blood pressures respectively) after reserpine treatment. This effect was suppressed by administration of RX-821002, a new specific α2-adrenoceptor antagonist. 6. Reserpine treatment significantly increased platelet α2-adrenoceptor number (identified with [3H]-yohimbine or [3H]-RX821002) with no change in K(d) values. α2-Adrenoceptor number remained unchanged in adipocytes (identified with [3H]-RX821002). 7. These results show that a 15 day treatment with reserpine induces a vascular α2-adrenergic supersensitivity and an up-regulation in platelet α2-adrenoceptors. In contrast, this phenomenon does not involve all the tissues since adipocyte α2-adrenoceptors escape the effect of reserpine. We suggest that the levels of plasma noradrenaline play an important role in the regulation of the platelet and vascular α2-adrenoceptors. In contrast, adipocyte α2-adrenoceptors are not affected by changes in plasma noradrenaline levels.