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

Abstract

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 μU/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.

Figure 1

Pregnancy impairs baroreflex control of heart rate by decreasing maximal gain and the maximal heart rate (see Table 1 for statistical comparison of baroreflex sigmoidal parameters).

Figure 2

Intracerebroventricular (icv) infusion of insulin increases baroreflex gain in pregnant but not virgin rats. Results of 3-way ANOVA revealed significant (P<0.05) group and time effects, as well as group by time, treatment by time, and group by treatment by time interactions. Con, control; insulin, following 1–2 hr icv insulin infusion; aCSF, following 1–2 hr icv aCSF infusion. N are numbers in the control bars. †, P<0.05 compared to virgin. *, P<0.05, within group effect of insulin or aCSF.

Figure 3

Intracerebroventricular infusion of insulin (top), but not aCSF (bottom), improves baroreflex gain in pregnant rats (see Table 2 and Figure 2 for statistical comparison of baroreflex sigmoidal parameters).

Figure 4

Representative experiment showing that icv insulin infusion increases baroreflex gain in a rat in late gestation.

Figure 5

Intracerebroventricular infusion of insulin (top) had no effect on the baroreflex in virgin rats, but aCSF (bottom) reduced the maximal heart rate and maximal baroreflex gain (see Table 2 and Figure 2 for statistical comparison of baroreflex sigmoidal parameters).