Exercise training improves peripheral chemoreflex function in heart failure rabbits.
June 29th, 2008 | by admin |Exercise training improves peripheral chemoreflex function in heart failure rabbits.
An enhancement of peripheral chemoreflex sensitivity contributes to sympathetic hyperactivity in chronic heart failure (CHF) rabbits. The enhanced chemoreflex function in CHF involves augmented carotid body (CB) chemoreceptor activity via upregulation of the angiotensin (Ang) II-AT1 receptor pathway and downregulation of the neuronal nitric oxide synthase (nNOS)-NO pathway in the CB. Here we investigated whether exercise training (EXT) normalizes the enhanced peripheral chemoreflex function in CHF rabbits and possible mechanisms mediating this effect. EXT partially but not fully normalized the exaggerated baseline renal sympathetic nerve activity (RSNA) and the response of RSNA to hypoxia in CHF rabbits. EXT also decreased the baseline carotid body nerve single-fiber discharge (4.9 +/- 0.4 vs. 7.7 +/- 0.4 imp/s at PO2 =103 +/- 2.3 mm Hg) and the response to hypoxia (20.6 +/- 1.1 vs. 36.3 +/- 1.3 imp/s at PO2 =41 +/- 2.2 mm Hg) from CB chemoreceptors in CHF rabbits, which could be reversed by treatment of the CB with Ang II or a nNOS inhibitor. Our results also showed that NO concentration and protein expression of nNOS were increased in the CBs from EXT + CHF rabbits, compared with that in CHF rabbits. On the other hand, elevated Ang II concentration and AT1 receptor overexpression of the CBs in CHF state were blunted by EXT. These results indicate that EXT normalizes the CB chemoreflex in CHF by preventing an increase in afferent CB chemoreceptor activity. EXT reverses the alterations in the nNOS-NO and Ang II-AT1 receptor pathways in the CB responsible for chemoreceptor sensitization in CHF. Key words: Angiotensin, Nitric oxide, Carotid Body, Chemoreceptor.
Li YL, Ding Y, Agnew C, Schultz HD.
University of Nebraska Medical Center.