EFFECT OF EARLY BLOCKADE OF BRADYKININ B-2-RECEPTORS ON THE BLOOD-PRESSURE PHENOTYPE OF NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS

We evaluated if chronic blockade of bradykinin B-2-receptors by the lo ng-acting antagonist Icatibant (D-Arg,[Hyp(3),Thi(5),D-Tic(7),Oic(8)]- bradykini) affects blood pressure of rats. Pairs of normotensive Wista r Kyoto rats or spontaneously hypertensive rats were mated and their o ffspring 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 admini stration of Icatibant or vehicle was continued by i.p. infusion using Alzet osmotic pumps. At 9 weeks of age, normotensive rats given Icatib ant showed greater systolic blood pressure (135 +/- 1 vs 115 +/- 1 mmH g in vehicle-treated rats, P < 0.01), while heart rate was similar. Th e group difference regarding blood pressure levels was confirmed by di rect intra-arterial measurement. No difference was detected between ve hicle-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 phe notype of Wistar Kyoto rats, provided that the antagonist is given at the early phases of life. These results suggest that the B-2-receptor is essential for the maintenance of cardiovascular homeostasis during development, whereas it does not exert a protective role against the p rogression of hypertension in a rat model of genetic hypertension. (C) 1997 The Italian Pharmacological Society.