The goal of this study was to test the hypothesis that administration of superoxide dismutase (SOD, an oxygen radical scavenger) restores impaired endothelium-dependent dilatation of rat skeletal muscle arterioles during chronic heart failure. Heart failure was induced in Sprague-Dawley rats by coronary artery ligation, which produced =40% infarction of the left ventricle. Four weeks following coronary artery ligation (n=7) or sham (control; n=5) surgery the spinotrapezius muscle was prepared for direct visualization of the microcirculation. Responses of third order arterioles (32.5±0.4 microns) to topical suffusion of the endothelium-dependent agonists acetylcholine and bradykinin and to the endothelium-independent agonist sodium nitroprusside were measured in both groups via intravital microscopy. Response of arterioles to acetylcholine was significantly less (p<0.05) in heart failure animals (0.1 μM = 3.8% and 1.0 μM = 10.2% change from baseline) as compared to control animals (0.1 μM = 15.5% and 1.0 μM = 32.6% change from baseline). Response of arterioles to bradykinin was significantly less (p<0.05) in heart failure animals (0.01 μM = 13.7% and 0.1 μM = 21.3% change from baseline) as compared to control animals (0.01 μM = 27.6% and 0.1 μM = 55.5% change from baseline). In contrast, response of arterioles to sodium nitroprusside (10 and 100 μM) was not different between groups (p>0.05). The impaired responses observed in heart failure animals could be partially restored by =38% towards that observed in controls following 30 minutes of a continuous topical suffusion of SOD (150 U/ml). SOD did not alter vasodilatory responses in control animals (p>0.05). Thus, it appears that altered production of oxygen radicals, to inactivate nitric oxide, may partially explain the impaired arteriolar reactivity observed during heart failure.
|Original language||English (US)|
|State||Published - 1997|
ASJC Scopus subject areas
- Molecular Biology