CALL FOR PAPERS Cardiovascular and Cerebrovascular Aging—New Mechanisms and Insights Endogenous leptin contributes to baroreflex suppression within the solitary tract nucleus of aged rats

Arnold AC, Diz DI. Endogenous leptin contributes to baroreflex suppression within the solitary tract nucleus of aged rats. Am J Physiol Heart Circ Physiol 307: H1539–H1546, 2014. First published September 26, 2014; doi:10.1152/ajpheart.00282.2014.—The decline in cardiovagal baroreflex function that occurs with aging is accompanied by an increase in circulating leptin levels. Our previous studies showed that exogenous leptin impairs the baroreflex sensitivity for control of heart rate in younger rats, but the contribution of this hormone to baroreflex dysfunction during aging is unknown. Thus we assessed the effect of bilateral leptin microinjection (500 fmol/60 nl) within the solitary tract nucleus (NTS) on the baroreflex sensitivity in older (66 2 wk of age) urethane/chloralose anesthetized SpragueDawley rats with elevated circulating leptin levels. In contrast to the 63% reduction observed in younger rats, leptin did not alter the baroreflex sensitivity for bradycardia evoked by phenylephrine in older rats (0.76 0.19 baseline vs. 0.71 0.15 ms/mmHg after leptin; P 0.806). We hypothesized that this loss of sensitivity reflected endogenous suppression of the baroreflex by elevated leptin, rather than cardiovascular resistance to the peptide. Indeed, NTS administration of a leptin receptor antagonist (75 pmol/120 nl) improved the baroreflex sensitivity for bradycardia in older rats (0.73 0.13 baseline vs. 1.19 0.26 at 10 min vs. 1.87 0.32 at 60 min vs. 1.22 0.54 ms/mmHg at 120 min; P 0.002), with no effect in younger rats. There was no effect of the leptin antagonist on the baroreflex sensitivity for tachycardia, responses to cardiac vagal chemosensitive fiber activation, or resting hemodynamics in older rats. These findings suggest that the actions of endogenous leptin within the NTS, either produced locally or derived from the circulation, contribute to baroreflex suppression during aging.