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(Hypertension. 1996;27:746-751.)
© 1996 American Heart Association, Inc.

Articles

Sexual Dimorphism of Cardiovascular Responses to Early Blockade of Bradykinin Receptors

Paolo Madeddu; Paolo Pinna Parpaglia; Vittorio Anania; Nicola Glorioso; Caroline Chao; Cindy Wang; Julie Chao

From the Clinica Medica (P.M., P.P.P., N.G.) and Farmacologia (V.A.), University of Sassari, Italy, and the Department of Biochemistry and Molecular Biology (C.C., C.W., J.C.), Medical University of South Carolina, Charleston.

Correspondence to Paolo Madeddu, MD, Clinica Medica, University of Sassari, Viale S. Pietro 8, 07100 Sassari, Italy.

Abstract To assess whether the cardiovascular effects induced by early blockade of bradykinin B₂-receptors with Hoe 140 (D-Arg[Hyp³,Thi⁵,D-Tic⁷,Oic⁸]-bradykinin) are influenced by sex, Wistar rats of both sexes received the antagonist (300 nmol/d per kilogram body wt) or vehicle from 2 days to 7 weeks of age by subcutaneous injection and then by intraperitoneal infusion. Compared with control rats, Hoe 140–treated female rats showed higher systolic blood pressure levels at 7 and 9 weeks of age (125±2 versus 111±2 mm Hg and 132±3 versus 116±2 mm Hg, respectively, P<.05), whereas in male rats a difference was found at 7 weeks (122±4 versus 108±4 mm Hg, P<.05) but not at 9 weeks. At this stage, the mean blood pressure of Hoe 140–treated rats was higher than that of control animals, and this difference was more pronounced at 12 weeks in female rats (121±2 versus 100±3 mm Hg in control animals, P<.01) compared with males (116±3 versus 104±2 mm Hg in control rats, P<.05). After the first week of life, body weight gain was greater in Hoe 140–treated female rats than in control rats, whereas a group-difference was detected in male rats only after weaning. In Hoe 140–treated female rats, heart weight was already increased at 9 weeks (330±6 versus 305±5 mg/100 g body wt in control rats, P<.05), whereas it was necessary to prolong Hoe 140 administration in male rats to develop heart hypertrophy (300±4 versus 275±4 mg/100 g body wt in control rats at 12 weeks, P<.05). Tissue kallikrein mRNA levels were higher in the kidney of adult female rats, whereas no sex difference was detected in the heart. The finding of a sexual dimorphism in the cardiovascular response to early blockade of bradykinin receptor suggests that endogenous kinins play a role in the regulation of cardiovascular function in both sexes, but they may be functionally more important in the female rat.

Key Words: kallikrein • sex characteristics • receptor, bradykinin

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