Myocardial hypertrophy, cardiac β‐adrenoceptors and adenylate cyclase activity during sinoaortic denervation in dogs

• Published in: British journal of pharmacology 1992-02, Vol.105 (2), p.341-346
• Main Authors: Galinier, Michel, Sénard, Jean‐Michel, Valet, Philippe, Dréan, Géraldine, Planat, Valerie, Arias, Agustin, Tran, Marie‐Antoinette, Montastruc, Jean‐Louis
• Format: Article
• Language: English
• Subjects: adenylate cyclase; Adenylyl Cyclases - metabolism; Animals; beta -adrenergic; Biological and medical sciences; Blood Pressure - physiology; Body Weight - physiology; cardiac hypertrophy; Cardiology. Vascular system; Cardiomegaly - physiopathology; catecholamines; Denervation; Dogs; Epinephrine - metabolism; Female; Heart; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Male; Medical sciences; Myocardium - cytology; Myocardium - enzymology; Myocardium - metabolism; Norepinephrine - metabolism; Organ Size - physiology; Receptors, Adrenergic, beta - drug effects; Receptors, Adrenergic, beta - metabolism; Sinoaortic denervation; Sinoatrial Node - physiology; β‐adrenoceptors
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1992.tb14256.x

Summary 1 . The long‐term effects of sinoaortic denervation on the development of left ventricular hypertrophy (assessed by the measurement of the ratio (R): heart weight/total body weight and LVT: left ventricular thickness), myocardial β‐adrenergic receptivity (measured by [125I]‐cyanopindolol binding and adenylate cyclase activity) and plasma catecholamine levels (measured by h.p.l.c.) were investigated in three groups of dogs: normotensive controls (group 1), dogs made hypertensive by sinoaortic denervation and evaluated 1 (group 2) and 18 months (group 3) later. 2 . Noradrenaline (NA) and adrenaline (A) plasma levels were 461 ± 54 and 85 ± 45 pg ml−1 in controls, 861 ± 185 and 191 ± 23 pg ml−1 in group 2 (P < 0.05). They were normal in group 3 (426 ± 132 and 110 ± 16 pg ml−1). 3 . R and LVT values were significantly (P < 0.05) higher in sinoaortic denervated dogs (R = 7.7 ± 0.1 and 7.8 ± 0.2; LVT = 13.6 ± 1.3 and 14.2 ± 0.9 mm in groups 2 and 3 respectively) than in normotensive dogs (group 1: R = 6.7 ± 0.1, LVT = 9.3 ± 0.8 mm). 4 . In group 1, the total number of β‐adrenoceptors (Bmax) was 37 ± 11 and 29 ± 6 fmol mg−1 protein in the left ventricle (LV) and right auricle (RA) respectively. In group 2, Bmax was significantly lower (10 ± 3 in LV and 13 ± 2 fmol mg−1 protein in RA, P < 0.05) than in group 1. There was no difference between group 1 and group 3 (37 ± 3 fmol mg−1 prot in LV and 31 ± 3 fmol mg−1 protein in RA). 5 . The percentage of β1‐adrenoceptors was 82 ± 4 in LV and 75 ± 5 in RA in group 1. It was significantly lower (P < 0.05) in groups 2 (LV: 33 ± 6 and RA: 33 ± 5) and 3 (LV: 59 ± 3 and RA: 55 ± 4). 6 . Basal values of adenylate cyclase activity in LV significantly decreased after sinoaortic denervation. Isoprenaline alone or in the presence of a β2‐adrenoceptor antagonist (ICI 118551, 1 μm) failed to stimulate adenylate cyclase activity 1 (but not 18) month after sinoaortic denervation. 7 . These data show that sinoaortic denervation is associated with left ventricular hypertrophy which appears early (1 month) and persists until 18 months despite the normalization of plasma catecholamine levels. The total number of myocardial β‐adrenoceptors is closely related to catecholamine levels but a selective decrease in β1‐adrenoceptors is observed during cardiac hypertrophy. The fall in basal adenylate cyclase activity suggests that cardiac hypertrophy is associated with an impairment of transmembrane signalling.