Vasoactive Potential of the B1 Bradykinin Receptor in Normotension and Hypertension

Abstract —The B 1 type receptor of bradykinin (Bk B 1 R) is believed to be physiologically inert but highly inducible by inflammatory mediators and tissue damage. To explore the potential participation of the Bk B 1 R in blood pressure (BP) regulation, we studied mice with deleted Bk B 2 R gene with induced experimental hypertension, either salt-dependent (subtotal nephrectomy with 0.5% NaCl as drinking water) or renin/angiotensin-dependent (renovascular 2-kidney–1-clip). Compared with the wild-type controls, the B 2 R 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 1 R 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 selective B 1 R agonist produced a dose-dependent hypotensive response in the knockout mice only. Assessment of tissue expression of B 1 R and B 2 R genes by reverse transcription–polymerase chain reaction techniques revealed significantly higher B 1 R mRNA levels in the B 2 R knockout mice at all times (normotensive baseline and hypertensive end points). At the hypertensive end points, there was always an increase in B 1 R gene expression over the baseline values. This increase was significant in cardiac and renal tissues in all hypertensive wild-type mice but only in the clipped kidney of the renovascular knockout mice. The B 2 R gene expression in the wild-type mice remained unaffected by experimental manipulations. These results confirm the known vasodilatory and natriuretic function of the Bk B 2 R; they also indicate that in its absence, the B 1 R can become upregulated and assume some of the hemodynamic properties of the B 2 R. Furthermore, they indicate that experimental manipulations to produce hypertension also induce upregulation of the B 1 R, but not the B 2 R, in cardiac and renal tissues.