Premium
Reserpine induces vascular α 2 ‐adrenergic supersensitivity and platelet α 2 ‐adrenoceptor up‐regulation in dog
Author(s) -
Estan Luis,
Senard JeanMichel,
Tran MarieAntoinette,
Montastruc JeanLouis,
Berlan Michel
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12710.x
Subject(s) - reserpine , medicine , endocrinology , yohimbine , clonidine , catecholamine , blood pressure , heart rate , adrenergic , antagonist , chemistry , receptor
1 The aim of the present study was to investigate the influence of catecholamine levels on the regulation of α 2 ‐adrenoceptor sensitivity in dogs. 2 Blood pressure and heart rate values at rest, plasma catecholamine levels, platelet and adipocyte α 2 ‐adrenoceptors as well as the α 2 ‐mediated cardiovascular responses to clonidine (10 μg kg −1 i.v., after α 1 ‐, β‐adrenoceptor plus muscarinic blockade) or noradrenaline (0.5, 1, 2 and 4 μg kg −1 i.v. after α 1 ‐ and β‐adrenoceptor blockade) were measured before and after reserpine treatment (0.1 mg kg −1 day −1 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 ± 3mmHg 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 performed 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 α 2 ‐mediated pressor responses 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 α 2 ‐adrenoceptor antagonist. 6 Reserpine treatment significantly increased platelet α 2 ‐adrenoceptor number (identified with [ 3 H]‐yohimbine or [ 3 H]‐RX821002) with no change in K d values. α 2 ‐Adrenoceptor number remained unchanged in adipocytes (identified with [ 3 H]‐RX821002). 7 These results show that a 15 day treatment with reserpine induces a vascular α 2 ‐adrenergic supersensitivity and an up‐regulation in platelet α 2 ‐adrenoceptors. In contrast, this phenomenon does not involve all the tissues since adipocyte α 2 ‐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 α 2 ‐adrenoceptors. In contrast, adipocyte α 2 ‐adrenoceptors are not affected by changes in plasma noradrenaline levels.