Insulin resistance and impaired baroreflex gain during pregnancy

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 292; no. 6; pp. R2188 - R2195
• Main Authors: Daubert, Daisy L, Chung, Mee-Young, Brooks, Virginia L
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.06.2007
• Subjects: Animals; Baroreflex - physiology; Blood pressure; Blood Pressure - physiology; Brain; Feedback - physiology; Female; Heart Rate - physiology; Hypothesis testing; Insulin; Insulin - blood; Insulin Resistance - physiology; Pregnancy; Pregnancy, Animal - physiology; Rabbits
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00614.2006

1 Oregon Health & Science University, Department of Physiology and Pharmacology, Portland, Oregon; and 2 The Catholic University of Korea, Department of Anesthesiology and Pain Medicine, Seoul, Korea Submitted 28 August 2006 ; accepted in final form 10 February 2007 Pregnancy decreases baroreflex gain, but the underlying mechanism is unclear. Insulin resistance, which has been associated with reduced transport of insulin into the brain, is a consistent feature of many conditions exhibiting impaired baroreflex gain, including pregnancy. Therefore, using conscious pregnant and nonpregnant rabbits, we tested the novel hypothesis that the pregnancy-induced impairment in baroreflex gain is due to insulin resistance and reduced brain insulin. Baroreflex gain was determined by quantifying changes in heart rate in response to stepwise steady-state changes in arterial pressure, secondary to infusion of nitroprusside and phenylephrine. We found that insulin sensitivity and baroreflex gain were strongly correlated in nonpregnant and term pregnant rabbits ( r 2 = 0.59). The decrease in insulin sensitivity and in baroreflex gain exhibited similar time courses throughout pregnancy, reaching significantly lower levels at 3 wk of gestation and remaining reduced at 4 wk (term is 31 days). Treatment of rabbits with the insulin-sensitizing drug rosiglitazone during pregnancy almost completely normalized baroreflex gain. Finally, pregnancy significantly lowered cerebrospinal fluid insulin concentrations. These data identify insulin resistance as a mechanism underlying pregnancy-induced baroreflex impairment and suggest, for the first time in any condition, that decreased brain insulin concentrations may be the link between reductions in peripheral insulin sensitivity and baroreflex gain. conscious rabbits; rosiglitazone; cerebrospinal fluid; insulin sensitivity Address for reprint requests and other correspondence: V. L. Brooks, Dept. of Physiology and Pharmacology, L-334, Oregon Health & Science Univ., 3181 SW Sam Jackson Park Rd., Portland, OR 97239 (e-mail: brooksv{at}ohsu.edu )