C. Emanueli et al., The bradykinin B-1 receptor and the central regulation of blood pressure in spontaneously hypertensive rats, BR J PHARM, 126(8), 1999, pp. 1769-1776
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 hypertens
ive rats (SHR), respectively. Intracerebroventricular (i.c.v.) injection of
1 nmol B-1 receptor agonist Lys-desArg(9)-BK significantly increased the B
P 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 o
f 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 me
an BP in SHR (by 9 +/- 2 mmHg the former and 14 +/- 3 mmHg the latter compo
und), but not in WKY. In SHR, the BP response to R715 was associated to tac
hycardia.
4 I.c.v. Captopril, a kininase inhibitor, increased the BP of SHR, this res
ponse being partially prevented by i.c.v. R715 and reversed into a vasodepr
essor effect by R715 in combination with the B-2 antagonist Icatibant.
5 I.c.v. antisense oligodeoxynucleotides (ODNs) targeted to the B-1 recepto
r mRNA decreased BP in SHR, but not in WKY. HR was not altered in either st
rain. Distribution of fluorescein-conjugated ODNs was detected in brain are
as surrounding cerebral ventricles.
6 Our results indicate that the brain B-1 receptor participates in the regu
lation of BP. Activation of the B-1 receptor by kinin metabolites could par
ticipate in the pathogenesis of hypertension in SHR.