Strain-dependent variation in vascular responses to nitric oxide in the isolated murine heart.
Numerous studies in the literature have employed gene-modified mice to investigate vascular function. However, only very limited information exists on baseline murine vascular physiology or on potential variations between different strains. We therefore compared coronary and aortic vascular responses to endothelium-derived vasodilators and exogenous nitric oxide (NO) in three commonly used mouse strains and correlated these data with expression of eNOS, NADPH oxidase subunits, gp91(phox) and p67(phox), and superoxide production. Isolated perfused hearts from MF1, 129sv and C57BL/6J mice were subjected to: (a) increasing doses of bradykinin, acetylcholine and sodium nitroprusside, and (b) bolus doses of adenosine and the NO synthase inhibitor, N(G)-monomethyl- L -arginine. Vascular responses of thoracic aortic rings were assessed for comparison. Expression of eNOS and NADPH oxidase subunits was assessed by immunoblotting, and superoxide production by lucigenin-enhanced chemiluminescence. Coronary vasodilator responses to bradykinin, acetylcholine and sodium nitroprusside were significantly attenuated in MF1 compared with C57BL/6J and 129sv hearts. Similarly, aortic relaxation to acetylcholine was significantly impaired in MF1 aortic rings compared with in C57BL/6J aortae; these differences were reversed by Tiron. N(G)-monomethyl- L -arginine induced significantly less vasoconstriction in MF1 and 129sv hearts compared with C57BL/6J. No differences in aortic relaxation to A23187 or sodium nitroprusside were observed. Cardiac and aortic superoxide production and cardiac expression of p67(phox) and gp91(phox) were significantly greater in MF1 mice compared with the other strains. There is significant strain-dependent variation in coronary and aortic vascular responsiveness in mice, which may reflect differences in the balance between NO and superoxide generation.
Bendall
Jennifer K
JK
Department of Cardiology, Guy's King's and St. Thomas' School of Medicine, King's College London, Denmark Hill Campus, Bessemer Road, London SE5 9PJ, UK.
Heymes
Christophe
C
Wright
Timothy J F
TJ
Wheatcroft
Stephen
S
Grieve
David J
DJ
Shah
Ajay M
AM
Cave
Alison C
AC
D000818:Animals; D001011:Aorta / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D003433:Crosses, Genetic; D020022:Genetic Predisposition to Disease; D006321:Heart / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009929:Organ Size; D013045:Species Specificity; D013481:Superoxides / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D013481:Superoxides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases