REDUCED MUSCARINIC CHOLINOCEPTOR DENSITY AND SENSITIVITY IN VARIOUS MODELS OF EXPERIMENTAL CARDIAC-HYPERTROPHY

1 In the present study we investigated functional and binding characte ristics of muscarinic receptors in experimental cardiac hypertrophy. 2 As models of cardiac hypertrophy we used hearts of spontaneously hype rtensive rats (SHR) and Wistar rats with surgically induced abdominal aorta stenosis (ASR). Wistar Kyoto rats (WKY) and sham operated Wistar rats were used as respective controls. 3 The hypertrophy was more pro nounced in hearts of ASR compared to SHR, although the mean arterial p ressure was found to be lower. 4 Isolated, perfused Langendorff heart preparations (paced with 5 Hz) from both groups of hypertrophied heart s were less sensitive to the muscarinic agonists oxotremorin and metha choline (P < 0.05, all n = 6) when compared with control organs. The m aximal reduction in contractile force induced by methacholine was 59.3 +/- 4.5% in SHR and 41.6 +/- 3.4% in ASR hearts versus 26.4 +/- 4.1% and 25.0 +/- 2.6% in control organs, respectively. 5 The density (fmol /mg protein(-1)) of muscarinic receptors in membrane homogenates of he arts from SHR (127.6 +/- 11.5) was unchanged, whereas in hearts from A SR (221.0 +/- 8.9) it was found to be reduced (P < 0.05) when compared to the respective controls (142.5 +/- 14.7 and 308.8 +/- 16.1, respec tively, all n = 6). 6 From the present data we conclude that cardiac h ypertrophy results in a loss of sensitivity towards muscarinic recepto r stimulation. A corresponding reduction of left ventricular receptor density could only be demonstrated in massively hypertrophied hearts o f ASR.