Decreased heart rate variability in transgenic mice overexpressing atrial [beta]1-adrenoceptors. Mansier, Pascale, Claire M[acute]edigue, Nathalie Charlotte, Christophe Vermeiren, Edouard Coraboeuf, Edith Deroubai, Elisabeth Ratner, Brigitte Chevalier, Jean Clairambault, Fran[cedilla]cois Carr[acute]e, Thierry Dahkli, Brigitte Bertin, Pascale Briand, Donny Strosberg, and Bernard Swynghedauw. Unit[acute]e 127-INSERM and IFR Circulation-Lariboisi[grave]ere, H[circumflex]opital Lariboisi[grave]ere, 41 bd de la Chapelle, 75010 Paris. France; NRIA Domaine de Voluceau. Rocquencourt, 75118 Le Chesnay, France; Laboratoire de Physiologie Cellulaire, Universit[acute]e Paris Sud, Orsay, France; Institute of Experimental Cardiology, Laboratory of Experimental Endocrinology, Moscow, Russia; Laboratoire de Physiologie M[acute]edicale. Facult[acute]e de M[acute]edecine, 2 Avenue du Professeur L[acute]eon Bernard, 35042 Rennes, France; Laboratoire d'Immunopharmacologie Mol[acute]eculaire and Laboratoire de G[acute]en[acute]etique et Pathologie Exp[acute]erimentale. Institut Cochin de G[acute]en[acute]etique Mol[acute]eculaire, 22 rue M[acute]echain, 75014 Paris, France
APStracts 3:0169H, 1996.
Heart Rate Variability, HRV, depends on various reflexes, including the baroreflex or respiratory reflex. Experimental studies have suggested that the sinoatrial node density in G protein-linked receptors may be involved. Transgenic mice, T, with a specific 8 x fold atrial overexpression of human [beta]1-AdrenoReceptor, [beta]1 -AR, have been generated in order to evaluate the role of the atrial [beta]1-AR density on HRV. The heart rate was monitored using telemetry and the signal was analysed using a quantitative time -frequency domain analysis, the smoothed pseudo Wigner-Ville method, and phase portrait maps. (i) Heart rate was unchanged, but the two normal components of HRV were decreased in T. T have an unshortened lifespan and no arrhythmias. (ii) Challenge of the animals by propranolol showed no modulation of the HRV in T as compared to controls. (iii) Isolated atrial strips from T had an increased basal contractility and no isoproterenol-induced inotropic effect. (iv) The basal level of cAMP production was lowered in T suggesting a shift in adenylate cyclase isoforms.

Received 9 April 1996; accepted in final form 9 April 1996.
APS Manuscript Number H1212-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96