Impaired Baroreceptor Reflex Function of Older ASrAOGEN Rats

Abstract

Generation of Ang-(1–7) in the dorsal medulla through pathways catalyzed by neprilysin and ACE2 decreases in Sprague-Dawley (SD) rats as they age. Further, we have shown that reduced tissue Ang-(1–7) in aging rats (~70 weeks) contributes to a 40% reduction in baroreceptor reflex control of heart rate associated with increased systolic blood pressure (SBP). On the other hand, transgenic rats with low brain angiotensinogen (ASrAOGEN) do not exhibit increases in SBP as they age. However, data on age-related changes in baroreflex function of ASrAOGEN rats is lacking. Therefore, we assessed baroreflex control of heart rate in Young (3 – 4 months) and Older (15 – 16 months) conscious male ASrAOGEN rats as the slope of the relationship between phenylephrine-induced increases in blood pressure and decreases in heart rate. The heart rate baroreflex was attenuated in Older rats compared to Young rats (1.6 ± 0.6, n = 8 vs 3.6 ± 1.0 msec/mmHg, n = 4, respectively; p< 0.05). Further, heart rate baroreflex sensitivity of older SD rats [0.7 ± 0.2 msec/mmHg (n = 7)] was significantly less than that of older ASrAOGEN rats. Thus, heart rate baroreflex sensitivity declined with age in ASrAOGEN rats but remained higher than that of older SD rats. Since neprilysin and ACE2 mRNAs and Ang-(1–7) forming activity of these enzymes tends to be reduced in medulla oblongata of older ASrAOGEN and SD rats in comparison to that of younger rats, we suggest that decline in local production of Ang-(1–7) contributes to attenuated baroreflex function of ASrAOGEN and SD rats as they age. Support: HL51952; AHA-MA 021515U