Resposta taquicárdica e controle autonômico no exercício físico em modelo genético de insuficiência cardíaca

Increase of sympathetic nervous activity and tachycardia at rest or during physical exertions are associated with increase of morbimortality, even in the absence of clinical signs of cardiac disease. Considering the importance of the alpha(2A)/alpha(2C)-adrenergic receptors in the modulation of the nervous activity and heart rate (HR), the present study uses a genetic model of cardiomyopathy induced by excess of circulating catecholamine in the gene inactivation of the alpha(2A)/alpha(2)-adrenergic receptors in mice (alpha(2A)/alpha 2CKO) to verify the HR response to physical exercise (PE), as well as the sympathetic-vagal control of the HR to PE. The hypothesis is that there would be exacerbated tachycardic response during PE in alpha(2A)/alpha 2CKO mice even when the cardiac function was still preserved at rest, being the alpha(2A)-adrenergic receptor the main reason for this response. Male mice of the C57Bl6J lineage, control (CO) and with gene inactivation for the a(2A) (alpha 2AKO), alpha(2C) alpha 2CKO) and alpha(2A)/alpha 2CKO receptors were submitted to tolerance to a physical exercise test. Two other groups of mice, CO and alpha(2A)/alpha 2CKO, were submitted to pharmacological blocking of the muscarinic and beta-adrenergic receptors as well as to progressive PE to assess the sympathetic-vagal contribution to PE tachycardia. Intolerance to physical exercise (1.220 +/- 18 and 1.460 +/- 34 vs. 2.630 +/- 42m, respectively) and higher tachycardia to PE (765 +/- 16 e 792 +/- 13 vs. 603 +/- 18 bpm, respectively) in the alpha 2CKO and alpha(2A)/alpha 2CKO vs. CO mice was observed. Moreover, the autonomic balance was altered in the alpha(2A)/alpha 2CKO mice by the sympathetic hyperactivity and lower cardiac vagal effect. These outcomes demonstrated the importance of the alpha(2A)/alpha(2C)-adrenergic receptors in autonomic control not only at rest, but also during PE, being the alpha(2A)-adrenergic receptor responsible for the sympathetic hyperactivity and lower vagal effect observed. This exacerbated tachycardic response in alpha(2A)/alpha 2CKO mice is present even when cardiac dysfunction is not observed.