Salt-sensitive hypertension in bradykinin B2 receptor knockout mice.
The kallikrein-kinin system regulates water and sodium excretion and thus plays a role in blood pressure (BP) homeostasis. We tested the hypothesis that mice lacking the gene encoding for the bradykinin B2 receptor (B2-KO) have a greater hypertensive response to chronic high Na+ intake (salt sensitivity) compared to controls. We also obtained dose-response curves for different vasoactive substances in both groups. The hypertensive effect of high Na+ intake was almost doubled in B2-KO mice compared to controls. A high-Na+ diet increased heart and kidney weight in B2-KO, but not in controls, suggesting an increased afterload in B2-KO mice. The BP response to bradykinin was completely abolished in B2-KO, but that to acetylcholine was conserved. The hypertensive response to angiotensin II was not exaggerated in B2-KO mice. This study describes a new salt-sensitive animal model and suggests that in mice kinins play a role in preventing salt-sensitive hypertension.
Alfie
M E
ME
Department of Medicine and Heart, Henry Ford Hospital, Detroit, Michigan 48202, USA.
Yang
X P
XP
Hess
F
F
Carretero
O A
OA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D006706:Homeostasis; D006973:Hypertension / Q000139:chemically induced* / Q000235:genetics* / Q000503:physiopathology; D016234:Kallikrein-Kinin System / Q000502:physiology; D007668:Kidney / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000235:genetics*; D012965:Sodium Chloride / Q000494:pharmacology*
D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D012965:Sodium Chloride; D000109:Acetylcholine; D001920:Bradykinin