Alterations in dynamic heart rate control in the b1-adrenergic receptor knockout mouse

Rohrer, Daniel K., Eric H. Schauble, Kavin H. Desai, Brian K. Kobilka, and Daniel Bernstein. Alterations in dynamic heart rate control in the b1-adrenergic receptor knockout mouse. Am. J. Physiol. 274 (Heart Circ. Physiol. 43): H1184–H1193, 1998.—b1-Adrenergic receptors (b1-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 b1-AR gene knockout model to test the hypothesis that b1-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 b1-AR knockouts and that the qualitative responses to baroreflex stimulation are intact. Chronotropic reserve in b1-AR knockouts is markedly limited, with peak heart rates ,200 beats/min less than wild types. During graded treadmill exercise, heart rate is significantly depressed in b1-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 b1-AR is not essential for either maintenance of resting heart rate or for maximally stressed cardiovascular performance.