Decreased heart rate variability in transgenic mice overexpressing atrial beta 1-adrenoceptors.
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, with a specific eightfold atrial overexpression of human beta 1-adrenoceptor (beta 1-AR), have been generated to evaluate the role of the atrial beta 1-AR density on HRV. The heart rate was monitored using telemetry, and the signal was analyzed using a quantitative time-frequency domain analysis, the smoothed pseudo-Wigner-Ville method, and phase portrait maps. 1) Heart rate was unchanged, but the two normal components of HRV were decreased in transgenic mice. Transgenic mice have an unshortened life span and no arrhythmias. 2) Challenge of the animals by propranolol showed no modulation of the HRV in transgenic mice compared with controls. 3) In isolated atrial strips from transgenic mice, basal contractility was increased and there was no isoproterenol-induced inotropic effect. 4) The basal level of adenosine 3',5'-cyclic monophosphate production was lowered in transgenic mice, suggesting a shift in adenylate cyclase isoforms.
Mansier
P
P
Unité 127 Institut National de la Santé et de la Recherche Médicale, Hôpital Lariboisière, Paris, France.
Médigue
C
C
Charlotte
N
N
Vermeiren
C
C
Coraboeuf
E
E
Deroubai
E
E
Ratner
E
E
Chevalier
B
B
Clairambault
J
J
Carré
F
F
Dahkli
T
T
Bertin
B
B
Briand
P
P
Strosberg
D
D
Swynghedauw
B
B
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D006325:Heart Atria; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D011433:Propranolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol