Published Online
on August 28, 2006

A more recent version of this article appeared on October 1, 2006

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Submitted on January 31, 2006
Revised on February 26, 2006

Hypertension Produced by Reductions in Uterine Perfusion in the Pregnant Rat. Role of Interleukin 6

Giovani Gadonski; B. Babbette D. LaMarca; Elizabeth Sullivan; William Bennett; Derrick Chandler; and Joey P. Granger^*

From the Departments of Physiology and Obstetrics-Gynecology and Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Miss.

^* To whom correspondence should be addressed. E-mail: jgranger{at}physiology.umsmed.edu.

Abstract--The purpose of this study was to determine the role of interleukin (IL) 6 in mediating the increase in arterial pressure (AP) in response to chronic reductions in uterine perfusion pressure (RUPP) in pregnant rats. AP was higher in RUPP rats (138±1 mm Hg) than in normal pregnant (NP) rats (104±1 mm Hg). Serum IL-6 levels in the RUPP rats were 104.5±28.6 pg/mL as compared with 36.6±7.4 pg/mL in NP rats. To determine the long-term effects of a 2- to 3-fold elevation in plasma IL-6 on renal function and AP in pregnant rats, we infused IL-6 for 5 days (2.5 ng/day) in NP rats starting at day 14 of gestation. Five days later, serum IL-6 levels were 55.5±6.5 pg/mL in the control NP rats and 157.0±36.1 pg/mL in the IL-6-treated NP rats. AP was higher in the IL-6-treated NP rats (115±3 mm Hg) as compared with NP controls (101±1 mm Hg) at day 19 of gestation. Renal plasma flow and GFR were lower in the IL-6-treated NP rats than in the NP group. IL-6 increased plasma renin activity but did not affect endothelin in IL-6-treated NP rats. In contrast to the NP rats, IL-6 had no effect on AP or renal hemodynamics in virgin rats. In summary, these data indicate that plasma IL-6 is elevated in response to chronic reductions in uterine perfusion in pregnant rats and that a comparable elevation in plasma IL-6 increases AP and reduces renal function in pregnant rats.

Key words: kidney • cytokines • hypertension • endothelin

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