Pregnancy impairs baroreflex control of heart rate in rats: role of insulin sensitivity

Abstract

Recent studies in rabbits suggest that insulin resistance and reduced brain insulin contribute to impaired baroreflex control of heart rate (HR) during pregnancy; however, the mechanisms are unknown. The rat model is ideal to investigate these mechanisms because much is known about rat brain baroreflex neurocircuitry and insulin receptor locations. However, it is unclear in rats whether pregnancy impairs the HR baroreflex or whether insulin resistance is involved. Therefore, this study tested the hypothesis that in rats pregnancy decreases HR baroreflex sensitivity (BRS) and that this decrease is related to concurrent decreases in insulin sensitivity (IS). BRS was quantified before, during, and after pregnancy using complementary methods: 1) spontaneous BRS (sBRS) derived from sequence method analysis of telemetric, continuous arterial pressure recordings; and 2) maximal BRS of complete sigmoidal baroreflex relationships. IS was measured (hyperinsulinemic euglycemic clamp) to determine whether BRS and IS change in parallel. sBRS was reduced at midgestation [pregnancy day 10 (P10)], returned to nonpregnant (NP) levels on P18, and fell again at late gestation (P20) (sBRS in ms/mmHg: NP, 1.66 ± 0.04; P10, 1.17 ± 0.11; P18, 1.55 ± 0.12; P20, 1.31 ± 0.05; n = 5; P < 0.05). Similar triphasic patterns were observed for both maximal BRS [in beats·min−1·mmHg−1: NP, 4.45 ± 0.52 ( n = 10); P11–12, 2.76 ± 0.11 ( n = 7); P17–18, 3.79 ± 0.14 ( n = 5); P19–20, 2.32 ± 0.40 ( n = 8); P < 0.0001] and previous and current measurements of IS (in mg glucose·kg−1·min−1: NP, 32 ± 2; P19–20, 15 ± 1; P < 0.0005). Furthermore, during pregnancy, the standard deviation (SD) of MAP increased, and the SD of HR decreased, indirectly suggesting baroreflex impairment. sBRS increased transiently during parturition, and sBRS, maximal BRS, and IS normalized 3–4 days postpartum. In conclusion, pregnancy decreases HR BRS in rats. The parallel temporal changes in BRS and IS suggest a mechanistic link.