Myocardial hypertrophy, cardiac beta-adrenoceptors and adenylate cyclase activity during sinoaortic denervation in dogs.
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 beta-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 less than 0.05). They were normal in group 3 (426 +/- 132 and 110 +/- 16 pg ml-1). 3. R and LVT values were significantly (P less than 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 beta-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 less than 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 beta 1-adrenoceptors was 82 +/- 4 in LV and 75 +/- 5 in RA in group 1. It was significantly lower (P less than 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.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 beta-adrenoceptors is closely related to catecholamine levels but a selective decrease in beta 1-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.
Galinier
M
M
Laboratoire de Pharmacologie Médicale et Clinique, INSERM U317, Faculté de Médecine, Toulouse, France.
Sénard
J M
JM
Valet
P
P
Dréan
G
G
Planat
V
V
Arias
A
A
Tran
M A
MA
Montastruc
J L
JL
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D006332:Cardiomegaly / Q000503:physiopathology*; D003714:Denervation; D004285:Dogs; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D009929:Organ Size / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012849:Sinoatrial Node / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases; D009638:Norepinephrine; D004837:Epinephrine