The bradykinin B 1 receptor and the central regulation of blood pressure in spontaneously hypertensive rats

• Published in: British journal of pharmacology Vol. 126; no. 8; pp. 1769 - 1776
• Main Authors: Emanueli, Costanza, Chao, Julie, Regoli, Domenico, Chao, Lee, Ni, Aiguo, Madeddu, Paolo
• Format: Journal Article
• Language: English
• Published: 29.01.2009
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0702527

We evaluated if the brain bradykinin (BK) B 1 receptor is involved in the regulation of blood pressure (BP) in conscious rats. 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. I.c.v. injection of 0.01 nmol B 1 antagonists, LysLeu 8 ‐desArg 9 ‐BK or AcLys[ D ‐βNal 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. 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. 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. 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. British Journal of Pharmacology (1999) 126 , 1769–1776; doi: 10.1038/sj.bjp.0702527