Vasoactive potential of the B-1 bradykinin receptor in normotension and hypertension

The B-1 type receptor of bradykinin (Bk B1R) is believed to be physiologica lly inert but highly inducible by inflammatory mediators and tissue damage. To explore the potential participation of the Bk B1R in blood pressure (BP ) regulation, we studied mice with deleted Bk B2R gene with induced experim ental hypertension, either salt-dependent (subtotal nephrectomy with 0.5% N aCl as drinking water) or renin/angiotensin-dependent (renovascular 2-kidne y-1-clip). Compared with the wild-type controls, the B2R gene knockout mice had a higher baseline BP (109.7+/-1.1 versus 101.1+/-1.3 mm Hg, P=0.002), developed salt-induced hypertension faster (in 19.3+/-2.3 versus 27.7+/-2.4 days, P=0.024), and had a more severe end point BP (148+/-3.7 versus 133+/ -3.1 mm Hg, P<0.05). On the contrary, renovascular hypertension developed t o the same extent (149.7+/-4.3 versus 148+/-3.6 mm Hg) and in the same time frame (14+/-2.2 versus 14+/-2.1 days). A bolus infusion of a selective B1R antagonist at baseline produced a significant hypertensive response (by 11 .4+/-2 mm Hg) in the knockout mice only. Injection of graded doses of a sel ective B1R agonist produced a dose-dependent hypotensive response in the kn ockout mice only. Assessment of tissue expression of B1R and B2R genes by r everse transcription-polymerase chain reaction techniques revealed signific antly higher B1R mRNA levels in the B2R knockout mice at all times (normote nsive baseline and hypertensive end points). At the hypertensive end points , there was always an increase in B1R gene expression over the baseline val ues. This increase was significant in cardiac and renal tissues in all hype rtensive wild-type mice but only in the clipped kidney of the renovascular knockout mice. The B2R gene expression in the wild-type mice remained unaff ected by: experimental manipulations. These results confirm the known vasod ilatory and natriuretic function of the Bk B2R; they also indicate that in its absence, the B1R can become upregulated and assume some of the hemodyna mic properties of the B2R. Furthermore, they indicate that experimental man ipulations to produce hypertension also induce upregulation of the B1R, but not the B2R, in cardiac and renal tissue.