Strain-dependent susceptibility for hypertension in mice resides in the natural killer gene complex.
Hypertension is associated with chronic vascular inflammation. We tested the hypothesis that the sensitivity to develop hypertension and vascular remodeling depends on the immunological background. Blood pressure, vascular remodeling, endothelial function, vascular architecture (number of collateral arteries), and expression of inflammatory cytokines were determined in mice that received N(G)-nitro-l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthesis. We studied C57BL/6, BALB/c, and BALB.B6-Cmv1r mice, a congenic strain where the natural killer (NK) gene complex of C57BL/6 mice is introduced in the BALB/c background. During a 4-wk treatment with l-NAME, blood pressure initially increased in both C57BL/6 and BALB/C mice, but after 4 wk, only C57BL/6 mice showed a significant increase in mean arterial blood pressure (+53 mmHg; P < 0.001) and small artery inward remodeling. Endothelial function and vascular design were significantly different between C57BL/6 mice and BALB/C mice. The inflammatory response was similar in C57BL/6 and BALB/C mice, except for the leukocyte marker CD11b. Cellular colocalization of CD11b with NK1.1 indicated the recruitment of NK cells in C57BL/6 mice. Congenic BALB.B6-Cmv1r mice showed the same endothelial response and vascular architecture as BALB/c mice. However, BALB.B6-Cmv1r mice displayed a similar sensitivity to hypertension and vascular remodeling as C57BL/6 mice. In conclusion, we have identified the NK gene complex as an important determinant in the genetically determined sensitivity to develop l-NAME-induced hypertension in mice.
Dept. of Biomedical Engineering and Physics, Academic Medical Ctr., Amsterdam, The Netherlands.
Zhila
Z
Taherzadeh
Ed
E
VanBavel
Judith
J
de Vos
Hanke L
HL
Matlung
Gert
G
van Montfrans
Lizzy M
LM
Brewster
Leonard
L
Seghers
Paul H A
PH
Quax
Erik N T P
EN
Bakker
D000818:Animals; D000950:Antigens, Ly / Q000235:genetics* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D039481:CD11b Antigen / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester / Q000009:adverse effects / Q000494:pharmacology; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000235:genetics* / Q000378:metabolism
D000950:Antigens, Ly; D039481:CD11b Antigen; D004791:Enzyme Inhibitors; C527211:Klrb1c protein, mouse; D055651:NK Cell Lectin-Like Receptor Subfamily B; D019331:NG-Nitroarginine Methyl Ester