Key result
Lack of iNOS in mice with DOCA-salt hypertension preserved cardiac function and reduced oxidative stress, but did not prevent hypertension and hypertrophy.
Why the study?
Does lack of iNOS preserve cardiac function and reduce oxidative stress in mice with DOCA-salt hypertension?
Does lack of iNOS preserve cardiac function and reduce oxidative stress in mice with DOCA-salt hypertension?
Lack of iNOS preserves cardiac function and enhances response to isoproterenol in a mouse model of DOCA-salt hypertension, likely via reduced oxidative stress, though it does not prevent hypertension or hypertrophy.
Although NO derived from endothelial NO synthase (eNOS) is thought to be cardioprotective, the role of inducible NO synthase (iNOS) remains controversial. Using mice lacking iNOS (iNOS-/-), we studied (1) whether development of hypertension, cardiac hypertrophy, and dysfunction after deoxycorticosterone acetate (DOCA)-salt would be less severe compared with wild-type controls (WT; C57BL/6J), and (2) whether the cardioprotection attributable to lack of iNOS is mediated by reduced oxidative stress. Mice were uninephrectomized and received either DOCA-salt (30 mg/mouse SC and 1% NaCl+0.2% KCl in drinking water) or vehicle (tap water) for 12 weeks. Systolic blood pressure (SBP) was measured weekly. Left ventricular (LV) ejection fraction (EF) by echocardiography and cardiac response to isoproterenol (50 ng/mouse IV) were studied at the end of the experiment. Expression of eNOS and iNOS as well as the oxidative stress markers 4-hydroxy-2-nonenal (4-HNE, a marker of lipid peroxidation) and nitrotyrosine (a marker for peroxynitrite) were determined by Western blot and immunohistochemical staining, respectively. DOCA-salt increased SBP and LV weight similarly in both strains and decreased EF in WT but not in iNOS-/-. Cardiac contractile and relaxation responses to isoproterenol were greater, 4-HNE and nitrotyrosine levels were lower, and eNOS expression tended to be higher in iNOS-/-. We conclude that lack of iNOS leads to better preservation of cardiac function, which may be mediated by reduced oxidative stress and increased eNOS; however, it does not seem to play a significant role in preventing DOCA-salt-induced hypertension and hypertrophy.
No takes yet. Share an insight, caveat, or question.
Sun et al. (2005) studied Deoxycorticosterone Acetate-Salt Hypertension. iNOS knockout (iNOS-/-) vs. Wild-type controls (WT; C57BL/6J) was evaluated on Systolic blood pressure, LV ejection fraction, cardiac response to isoproterenol, and oxidative stress markers. Lack of iNOS in mice with DOCA-salt hypertension preserved cardiac function and reduced oxidative stress, but did not prevent hypertension and hypertrophy.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: