title: Cardiovascular phenotypes of kinin B2 receptor- and tissue kallikrein-deficient mice.
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.
authors.affiliation: Département de Pharmacologie, Faculté de Médecine Paris-Sud, INSERM 00-01, Le Kremlin-Bicêtre, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Trabold
authors.forename: Sandrine
authors.initials: S
authors.lastname: Pons
authors.forename: Albert A
authors.initials: AA
authors.lastname: Hagege
authors.forename: May
authors.initials: M
authors.lastname: Bloch-Faure
authors.forename: François
authors.initials: F
authors.lastname: Alhenc-Gelas
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Giudicelli
authors.forename: Christine
authors.initials: C
authors.lastname: Richer-Giudicelli
authors.forename: Pierre
authors.initials: P
authors.lastname: Meneton
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015152:Blotting, Northern; D001920:Bradykinin / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006352:Heart Ventricles / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006706:Homeostasis / Q000235:genetics; D007610:Kallikreins / Q000172:deficiency* / Q000235:genetics; D007649:Ketamine / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009638:Norepinephrine / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D043782:Receptor, Bradykinin B2; D011945:Receptors, Angiotensin / Q000235:genetics; D018002:Receptors, Bradykinin / Q000172:deficiency* / Q000235:genetics; D012039:Regional Blood Flow / Q000187:drug effects; D012083:Renin / Q000235:genetics; D016276:Ventricular Function; D014991:Xylazine / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D043782:Receptor, Bradykinin B2; D011945:Receptors, Angiotensin; D018002:Receptors, Bradykinin; D000804:Angiotensin II; D014991:Xylazine; D007649:Ketamine; D007610:Kallikreins; D012083:Renin; D001920:Bradykinin; D009638:Norepinephrine