Impaired baroreflex gain during pregnancy in conscious rats: role of brain insulin

Pregnancy impairs baroreflex gain, but the mechanism is incompletely understood. To test the hypothesis that reductions in brain insulin contribute, we determined whether pregnant rats exhibit lower cerebrospinal fluid (CSF) insulin concentrations and whether intracerebroventricular infusion of insulin normalizes gain of baroreflex control of heart rate in conscious pregnant rats. CSF insulin was lower in pregnant (68 ± 21 pg/mL) compared to virgin (169 ± 25 pg/mL) rats (P < 0.05). Pregnancy reduced baroreflex gain (pregnant 2.4 ± 0.2 bpm/mm Hg, virgin 4.6 ± 0.3 bpm/mm Hg; P < 0.0001) and the maximum heart rate elicited by hypotension (pregnant 455 ± 15 bpm, virgin 507 ± 12 bpm; P = 0.01). Infusion of insulin (100 microU/min) intracerebroventricularly increased baroreflex gain in pregnant (2.4 ± 0.4 to 3.9 ± 0.5 bpm/mm Hg; P < 0.01) but not virgin (4.6 ± 0.4 to 4.2 ± 0.4 bpm/mm Hg; NS) rats. Maximum heart rate was not altered by intracerebroventricular insulin in either group. Interestingly, while in pregnant rats the baroreflex was unchanged by intracerebroventricular infusion of the artificial CSF vehicle, in virgin rats, vehicle infusion lowered baroreflex gain (4.7 ± 0.3 to 3.9 ± 0.3 bpm/mm Hg; P < 0.05) and the maximum baroreflex heart rate (495 ± 19 to 444 ± 21 bpm; P < 0.05). These data support the hypothesis that brain insulin is required to support optimal baroreflex function and that a decrease in brain insulin contributes to the fall in baroreflex gain during pregnancy.