title: Tissue kallikrein deficiency and renovascular hypertension in the mouse.
abstract: The kallikrein kinin system (KKS) is involved in arterial and renal functions. It may have an antihypertensive effect in both essential and secondary forms of hypertension. The role of the KKS in the development of two-kidneys, one-clip (2K1C) hypertension, a high-renin model, was investigated in mice rendered deficient in tissue kallikrein (TK) and kinins by TK gene inactivation (TK-/-) and in their wild-type littermates (TK+/+). Four weeks after clipping the renal artery, blood flow was reduced in the clipped kidney (2K1C-TK+/+: -90%, 2K1C-TK-/-: -93% vs. sham-operated mice), and the kidney mass had also decreased (2K1C-TK+/+: -65%, 2K1C-TK-/-: -66%), whereas in the unclipped kidney, blood flow (2K1C-TK+/+: +19%, 2K1C-TK-/-: +17%) and kidney mass (2K1C-TK+/+: +32%, 2K1C-TK-/-: +30%) had both increased. The plasma renin concentration (2K1C-TK+/+: +78%, 2K1C-TK-/-: +65%) and renal renin content of the clipped kidney (2K1C-TK+/+: +58%, 2K1C-TK-/-: +65%) had increased significantly. There was no difference for these parameters between 2K1C-TK+/+ and 2K1C-TK-/- mice. Blood pressure monitored by telemetry and by plethysmography, rose immediately after clipping in both genotypes, and reached similar levels (2K1C-TK+/+: +24%, 2K1C-TK-/-: +21%). 2K1C-TK+/+ and 2K1C-TK-/- mice developed similar concentric left ventricular hypertrophy (+24% and +17%, respectively) with normal cardiac function. These findings suggest that in the context of chronic unilateral reduction in renal blood flow, TK and kinins do not influence the trophicity of kidneys, the synthesis and secretion of renin, blood pressure increase, and cardiac remodeling due to renin angiotensin system activation.
authors.affiliation: INSERM U872, Centre de Recherche des Cordeliers, 75270 Paris, France.
authors.forename: Violaine
authors.initials: V
authors.lastname: Griol-Charhbili
authors.forename: Laurent
authors.initials: L
authors.lastname: Sabbah
authors.forename: Juliana
authors.initials: J
authors.lastname: Colucci
authors.forename: Marie-Pascale
authors.initials: MP
authors.lastname: Vincent
authors.forename: Véronique
authors.initials: V
authors.lastname: Baudrie
authors.forename: Dominique
authors.initials: D
authors.lastname: Laude
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Elghozi
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Nicolas
authors.initials: N
authors.lastname: Picard
authors.forename: Pierre
authors.initials: P
authors.lastname: Meneton
authors.forename: François
authors.initials: F
authors.lastname: Alhenc-Gelas
authors.forename: Christine
authors.initials: C
authors.lastname: Richer
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology; D004195:Disease Models, Animal; D006978:Hypertension, Renovascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000378:metabolism; D007705:Kinins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012039:Regional Blood Flow / Q000502:physiology; D012077:Renal Artery / Q000503:physiopathology; D012083:Renin / Q000378:metabolism; D020840:Tissue Kallikreins / Q000235:genetics*; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D007705:Kinins; D020840:Tissue Kallikreins; D012083:Renin