Sexual dimorphism of cardiovascular responses to early blockade of bradykinin receptors

To assess whether the cardiovascular effects induced by early blockade of bradykinin B-2-receptors with Hoe 140 (D-Arg[Hyp(3),Thi(5),D-Tic(7),Oic(8)]-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 mmHg 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.