Published Online
on June 10, 2002

A more recent version of this article appeared on July 1, 2002

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Submitted on March 27, 2002
Revised on April 17, 2002

Cardiovascular Phenotypes of Kinin B₂ Receptor-- and Tissue Kallikrein--Deficient Mice

Fabien Trabold; Sandrine Pons; Albert A. Hagege; May Bloch-Faure; François Alhenc-Gelas; Jean-François Giudicelli; Christine Richer-Giudicelli^*; and Pierre Meneton

From the Département de Pharmacologie, Faculté de Médecine Paris-Sud, INSERM 00-01 (F.T., S.P., J-F.G., C.R-G.), Le Kremlin-Bicêtre, France; Faculté de Médecine Necker-Enfants Malades, Université Paris (V A.A.H.), Paris, France; and INSERM U367 (M.B-F., F.A-G., P.M.), Paris, France.

^* To whom correspondence should be addressed. E-mail: pmeneton{at}infobiogen.fr .

Abstract—To clarify the role of the kallikrein-kinin system in cardiovascular homeostasis, the systemic and regional hemodynamics of kinin B₂ receptor--deficient (B₂^-/-) and tissue kallikrein--deficient (TK^-/-) mice were compared with their wild-type (WT) littermates on a pure C57BL/6 genetic background. B₂^-/-, TK^-/-, 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 B₂^-/- mice compared with TK^-/- and WT mice. In addition, B₂^-/- mice, but not TK^-/- 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. B₂^-/- mice were significantly more sensitive than were TK^-/- mice to the vasoconstrictor effects of angiotensin II and norepinephrine. Finally, renin mRNA levels were significantly greater in B₂^-/- mice and smaller in TK^-/- mice compared with WT mice. Taken together, these results indicate that under basal conditions, the kinin B₂ 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^-/- and B₂^-/- mice could be underlain by tissue kallikrein kinin--independent effect and/or kinin B₁ receptor activation.

Key words: kallikrein-kinin system • renin-angiotensin system • blood pressure • cardiac function • blood flow • mice

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