Effect of early blockade of bradykinin B2-receptors on the blood pressure phenotype of normotensive and spontaneously hypertensive rats

We evaluated if chronic blockade of bradykinin B₂-receptors by the long-acting antagonist Icatibant (D-Arg,[Hyp³,Thi⁵,D-Tic⁷,Oic⁸]-bradykin) affects blood pressure of rats. Pairs of normotensive Wistar Kyoto rats or spontaneously hypertensive rats were mated and their offspring received Icatibant (25 nmol day^-1 per kg body wt., s.c.) or vehicle from the 2nd day until the 7th week of life. Then, the administration of Icatibant or vehicle was continued by i.p. infusion using Alzet osmotic pumps. At 9 weeks of age, normotensive rats given Icatibant showed greater systolic blood pressure (135 ± 1 vs 115 ± 1 mmHg in vehicle-treated rats, P <0.01), while heart rate was similar. The group difference regarding blood pressure levels was confirmed by direct intra-arterial measurement. No difference was detected between vehicle- and Icatibant-treated spontaneously hypertensive rats regarding blood pressure increase with aging. In conclusion, chronic blockade of bradykinin receptors by Icatibant alters the adult cardiovascular phenotype of Wistar Kyoto rats, provided that the antagonist is given at the early phases of life. These results suggest that the B₂-receptor is essential for the maintenance of cardiovascular homeostasis during development, whereas it does not exert a protective role against the progression of hypertension in a rat model of genetic hypertension.