TY - JOUR
T1 - The bradykinin B1 receptor and the central regulation of blood pressure in spontaneously hypertensive rats
AU - Emanueli, Costanza
AU - Chao, Julie
AU - Regoli, Domenico
AU - Chao, Lee
AU - Ni, Aiguo
AU - Madeddu, Paolo
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Brain
KW - DNA
KW - Fluorescence
KW - Genetic
KW - Hypertension
KW - Kinins
UR - http://www.scopus.com/inward/record.url?scp=0033114049&partnerID=8YFLogxK
U2 - 10.1038/sj.bjp.0702527
DO - 10.1038/sj.bjp.0702527
M3 - Article
C2 - 10372819
AN - SCOPUS:0033114049
SN - 0007-1188
VL - 126
SP - 1769
EP - 1776
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 8
ER -