Sexual dimorphism of cardiovascular responses to early blockade of bradykinin receptors.
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 animals, 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.
Madeddu
P
P
Clinica Medica, University of Sassari, Italy.
Pinna Parpaglia
P
P
Anania
V
V
Glorioso
N
N
Chao
C
C
Wang
C
C
Chao
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D065168:Bradykinin Receptor Antagonists; D002320:Cardiovascular Physiological Phenomena; D005260:Female; D007610:Kallikreins / Q000032:analysis; D008297:Male; D051381:Rats; D018002:Receptors, Bradykinin / Q000502:physiology*; D012727:Sex Characteristics
D065168:Bradykinin Receptor Antagonists; D018002:Receptors, Bradykinin; C065679:icatibant; D007610:Kallikreins; D001920:Bradykinin