Sexual Dimorphism of Cardiovascular Responses to Early Blockade of Bradykinin Receptors

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.