The bradykinin B1 receptor and the central regulation of blood pressure in spontaneously hypertensive rats

1 We evaluated if the brain bradykinin (BK) B-1 receptor is involved in the regulation of blood pressure (BP) in conscious rats. 2 Basal mean BP and HR were 115 +/- 2 and 165 +/- 3 mmHg and 345 +/- 10 and 410 +/- 14 beats min(-1) in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR), respectively. Intracerebroventricular (i.c.v.) injection of 1 nmol B-1 receptor agonist Lys-desArg(9)-BK significantly increased the BP of WKY and SHR by 7 +/- 1 and 19 +/- 2 mmHg, respectively. One nmol Sar[D-Phe(8)]-desArg(9)-BK, a kininase-resistant B-1 agonist, increased the BP of WKY and SHR by 19 +/- 2 and 17 +/- 2 mmHg, respectively and reduced HR in both strains. 3 I.c.v. injection of 0.01 nmol B-1 antagonists, Lys-Leu(8)-desArg(9)-BK or AcLys[D-beta Nal(7),Ile(8)]desArg(9)-BK (R715), significantly decreased mean BP in SHR (by 9 +/- 2 mmHg the former and 14 +/- 3 mmHg the latter compound), but not in WKY. In SHR, the BP response to R715 was associated to tachycardia. 4 I.c.v. Captopril, a kininase inhibitor, increased the BP of SHR, this response being partially prevented by i.c.v. R715 and reversed into a vasodepressor effect by R715 in combination with the B-2 antagonist Icatibant. 5 I.c.v. antisense oligodeoxynucleotides (ODNs) targeted to the B-1 receptor mRNA decreased BP in SHR, but not in WKY. HR was not altered in either strain. Distribution of fluorescein-conjugated ODNs was detected in brain areas surrounding cerebral ventricles. 6 Our results indicate that the brain B-1 receptor participates in the regulation of BP. Activation of the B-1 receptor by kinin metabolites could participate in the pathogenesis of hypertension in SHR.