Mechanism of Cardiac Involvement in the WBN/Kob Rat

The cardiac characteristics of the WBN/Kob rat resemble those of rats with catecholamine-induced myocarditis. To determine the etiology of these WBN cardiac characteristics, we assessed the number and affinity ofβ-adrenergic receptors, and investigated adenylate cyclase activity, the cardiac myocyte cyclic adenosine monophosphate (cAMP) concentration and the activity of guanosine triphosphate (GTP)-binding protein in 3-month-old WBN/Kob rats. Age-matched Wistar rats served as controls. The mean number ofβ-adrenergic receptors was similar in WBN/Kob and Wistar rats (28.0±9.1v28.3±8.9 fmol/mg protein), and there was no significant difference inβ-adrenergic receptor affinity between groups (1.09±0.54v1.26±0.60 n ). The mean cAMP concentration in cardiac myocytes was significantly higher in WBN/Kob rats than in Wistar rats (975.6±247.8v344.9±83.6 pmol/g wet tissue), (P=0.0112) as was adenylate cyclase activity (33.61±8.32v24.3±12.78 pmol/mg/min), (P=0.0174). The activity of GTP-binding protein was significantly higher in WBN/Kob rats than in Wistar rats. After aβ-agonist binds to aβ-adrenergic receptor, activated adenylate cyclase produces cAMP in myocytes, which in turn opens the Ca2+channel, leading to an influx of Ca2+into myocytes. Our results suggest that the increase in adenylate cyclase activity in WBN/Kob rats have led to an increase in the cAMP concentration in myocytes. This process may have resulted in excessiveβ-adrenergic activity due to high activity of GTP binding protein in WBN/Kob rats, which may explain the hypersensitivity of WBN/Kob rats to isoproterenol and the development of catecholamine-induced myocarditis.