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 Sprague-Dawley 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.