Decreased insulin sensitivity: mechanism for decreased baroreflex gain during pregnancy?

Abstract

Baroreflex gain (BRG) decreases with pregnancy, but the underlying mechanism is unclear. We previously reported that the decreases in BRG and insulin sensitivity (IS) observed at term in conscious rabbits are correlated, suggesting the two are causally related. To further test this hypothesis, we determined if the changes in IS and BRG are temporally related within animals throughout gestation. In addition, we studied rabbits when they were non-pregnant (NP), pregnant (P), and then P treated with the insulin-sensitizing drug rosiglitazone (Rosi), to determine if prevention of the pregnancy-induced decrease in IS would increase BRG. BRG was assessed by sigmoidal fit of heart rate responses to changes in blood pressure due to iv infusion of increasing doses of nitroprusside or phenylephrine. IS was measured the following day using the hyperinsulinemic-euglycemic method. At 2 weeks of pregnancy neither BRG (57 ± 13 bpm/mmHg) nor IS (9.4 ± 1.4 mg glucose/kg/min) were different from NP (85 ± 9 bpm/mmHg; 10.4 ± 0.7 mg glucose/kg/min). At 3 weeks, both BRG (37 ± 5 bpm/mmHg, p<0.05) and IS (6.2 ± 0.6 mg glucose/kg/min, p<0.01) were reduced. BRG (16 ± 4 bpm/mmHg, p<0.01) and IS (5.0 ± 0.9 mg glucose/kg/min, p<0.01) remained decreased at 4 weeks (gestation is 31 days). These temporal changes in BRG and IS were well correlated (p<0.005, r2=0.53, n=4). Treatment of rabbits with Rosi throughout pregnancy prevented the decrease in IS (P=3.8 ± 0.1, P+Rosi=8.3 ± 0.5 mg glucose/kg/min; p<0.05, n=3) and increased BRG (P=13 ± 3, P+Rosi=36 ±11 bpm/mmHg; p<0.05, n=3). These data further support our novel hypothesis that the decrease IS during pregnancy contributes to the decrease in BRG. Supported by AHA 0315254Z, HL70962.