Modulation of kinin B1 receptor expression by endogenous angiotensin II in hypertensive rats.
We investigated the expression and localization of B1 receptor in tissues of rats submitted to a renin-dependent model of hypertension (2K-1C), and analyzed the influence of endogenous Ang II in modulating the in vivo expression of these receptors. B1 mRNA levels in the heart, kidney and thoracic aorta were quantified by real time PCR, B1 receptor protein expression was assessed by immunohistochemistry, plasma Ang II levels were analyzed by radioimmunoassay and the effects of AT1 receptor blockade were determined after losartan treatment. 2K-1C rats presented a marked increase in Ang II levels when compared to sham-operated rats. In parallel, cardiac- (but not renal and aortic) B1 mRNA levels were 15-fold higher in 2K-1C than in sham rats. In 2K-1C, B1 expression was detected in the endothelium of small cardiac arteries and in cardiomyocytes. Losartan completely reverted the increased B1 mRNA levels and significantly decreased the protein expression observed in 2K-1C rats, despite reducing, but not normalizing blood pressure. We conclude that in the 2K-1C rat, induction of cardiac B1 receptor might be tightly linked to AT1 receptor activation. These data suggest the existence of a new site of interaction between kinins and angiotensins, and might provide important contributions for a better understanding of the pathophysiology of hypertension.
Fernandes
Liliam
L
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, SP 05508-900, Brazil. liliamfe@usp.br
Ceravolo
Graziela S
GS
Fortes
Zuleica B
ZB
Tostes
Rita
R
Santos
Robson A S
RA
Santos
Jerusa A
JA
Mori
Marcelo A S
MA
Pesquero
João Bosco
JB
de Carvalho
Maria Helena C
MH
D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D005786:Gene Expression Regulation; D006973:Hypertension / Q000473:pathology; D007668:Kidney / Q000378:metabolism; D007705:Kinins / Q000096:biosynthesis*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D007705:Kinins; D012333:RNA, Messenger; D000804:Angiotensin II; D019808:Losartan