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

1. We evaluated if the brain bradykinin (BK) B₁ 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 B₁ receptor agonist Lys-desArg⁹-BK significantly increased the BP of WKY and SHR by 7 ± 1 and 19 ± 2 mmHg, respectively. One nmol Sar[D-Phe⁸]-desArg⁹-BK, a kininase-resistant B₁ 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 B₁ antagonists, LysLeu⁸-desArg⁹-BK or AcLys[D-βNal⁷,Ile⁸]-desArg⁹-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 B₂ antagonist Icatibant. 5. I.c.v. antisense oligodeoxynucleotides (ODNs) targeted to the B₁ 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 B₁ receptor participates in the regulation of BP. Activation of the B₁ receptor by kinin metabolites could participate in the pathogenesis of hypertension in SHR.