Abstract-To clarify the role of the kallikrein-kinin system in cardiovascular homeostasis, the systemic and regional hemodynamics of kinin B 2 receptor-deficient (B 2 Ϫ/Ϫ ) and tissue kallikrein-deficient (TK Ϫ/Ϫ ) mice were compared with their wild-type (WT) littermates on a pure C57BL/6 genetic background. B 2 Ϫ/Ϫ , TK Ϫ/Ϫ , and WT adult mice were normotensive and displayed normal hemodynamic (left ventricular [LV] pressure, cardiac output, total peripheral resistance, dP/dt max ) and echocardiographic (septum and LV posterior wall thickness, LV diameter, LV mass, and LV fractional shortening) parameters. However, heart rate was lower in B 2 Ϫ/Ϫ mice compared with TK Ϫ/Ϫ and WT mice. In addition, B 2 Ϫ/Ϫ mice, but not TK Ϫ/Ϫ mice, exhibited lower coronary and renal blood flows and greater corresponding vascular resistances than did WT mice, indicating a tonic physiological vasodilating effect of bradykinin in these vascular beds. However, maximal coronary vasodilatation capacity, estimated after dipyridamole infusion, was similar in the 3 groups of mice. B 2 Ϫ/Ϫ mice were significantly more sensitive than were TK Ϫ/Ϫ mice to the vasoconstrictor effects of angiotensin II and norepinephrine. Finally, renin mRNA levels were significantly greater in B 2 Ϫ/Ϫ mice and smaller in TK Ϫ/Ϫ mice compared with WT mice. Taken together, these results indicate that under basal conditions, the kinin B 2 receptor is not an important determinant of blood pressure in mice but is involved in the control of regional vascular tone in the coronaries and the kidneys. The phenotypic differences observed between TK Ϫ/Ϫ and B 2 Ϫ/Ϫ mice could be underlain by tissue kallikrein kinin-independent effect and/or kinin B 1 receptor activation. Key Words: kallikrein-kinin system Ⅲ renin-angiotensin system Ⅲ blood pressure Ⅲ cardiac function Ⅲ blood flow Ⅲ mice K inins are generated from enzymatic cleavage of circulating kininogens by serine proteases such as tissue kallikrein and exert their biological effects through activation of G protein-coupled B 1 and B 2 receptors. 1 In particular, the B 2 receptor is constitutively expressed in the vascular endothelium and mediates the vasodilator effects of kinins. 2 Its role in cardiovascular homeostasis has recently been assessed by the use of B 2 receptor-deficient (B 2 Ϫ/Ϫ ) mice, but there are significant discrepancies in the literature regarding the phenotype of these mice. Thus, the lack of B 2 receptor has been reported to induce either permanent 3-5 or transient hypertension, 6 to induce no hypertension unless the mice are fed a high-salt diet, 7,8 or to never induce hypertension, even on high salt intake. 9 These discrepancies may be explained in part by differences in the genetic background of B 2 Ϫ/Ϫ mice, which was 129Sv, 129SvEvTac, or C57BL/6. More problematic, they could also result from the fact that control mice were not littermates but mice issued from separate strains chosen to match the genetic background of B 2 Ϫ/Ϫ mice. It is known that in these conditions, a genetic shift in m...