Alterations in dynamic heart rate control in the beta 1-adrenergic receptor knockout mouse.
beta 1-Adrenergic receptors (beta 1-ARs) are key targets of sympathetic nervous system activity and play a major role in the beat-to-beat regulation of cardiac chronotropy and inotropy. We employed a beta 1-AR gene knockout model to test the hypothesis that beta 1-AR function is critical for maintenance of resting heart rate and baroreflex responsiveness and, on the basis of its important role in regulating chronotropy and inotropy, is also required for maximal exercise capacity. Using an awake unrestrained mouse model, we demonstrate that resting heart rate and blood pressure are normal in beta 1-AR knockouts and that the qualitative responses to baroreflex stimulation are intact. Chronotropic reserve in beta 1-AR knockouts is markedly limited, with peak heart rates approximately 200 beats/min less than wild types. During graded treadmill exercise, heart rate is significantly depressed in beta 1-AR knockouts at all work loads, but despite this limitation, there are no reductions in maximal exercise capacity or metabolic indexes. Thus, in mice, the beta 1-AR is not essential for either maintenance of resting heart rate or for maximally stressed cardiovascular performance.
Rohrer
D K
DK
Department of Pediatrics, Stanford University, California 94305, USA.
Schauble
E H
EH
Desai
K H
KH
Kobilka
B K
BK
Bernstein
D
D
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000502:physiology*; D018738:Hexamethonium / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout / Q000235:genetics* / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D014630:Vagus Nerve / Q000502:physiology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D005730:Ganglionic Blockers; D011943:Receptors, Adrenergic, beta; D018738:Hexamethonium