Effect of Dobutamine and Hyperoxia on Free Radicals Production in Relation to the Ultrastructural Alterations in the Endothelial of Myocardial Capillary in Rats, Rattus norvigicus

Abstract

Hyperoxia has been widely used as model for oxidative stress. Free radicals (FR), suproxide anion (*O2-) and nitric oxide anion (*NO−), are highly toxic and have detrimental effects on nitroso-redox balance in the myocyte. Myocardium is rich with β-adrenergic receptors and endothelial is the site of NO production. The authors hypothesized that graded doses of dobutamine result in hyperkinetic state, which shifts the nitroso-redox balance toward the buildup of reactive species in dose-dependent excess. The purpose of the present study was to investigate free radicals production and coronary endothelial cell pathological changes following increasing length of breathing oxygen (100% O2) and progressive doses of dobutamine. Thirty-five adult male rats, matched with age and body weight, were randomly assigned to 7 groups. The first group served as control (C) and the 2nd, 3rd, and 4th groups were exposed to hyperoxia (100% O2 breathing) for 24,48, and 72 h, whereas the 5th, 6th, and 7th groups were injected dobutamine 10,20, and 30 μg kg−1, respectively. Following the treatment condition for each group, animals were sacrificed and heart tissues were divided randomly into two parts. The first part was processed for the ultrastructure, using transmission electron microscope (TEM), and the second was homogenized for FR determination. TEM examination showed that O2 breathing for 24 h resulted in hypertrophy and proliferation of endothelial cells lining the coronary capillary, which was lodged by lymphoid cells. Distended and irregular contour of endothelium, enlarged nucleus, protrusion membrane, as well as pinocytotic vesicles were also observed. Free radicals (FR) production at all levels of hyperoxia exposures and dobutamine injections were significantly (p < .05) higher than control group. In addition, dobutamine induced higher relative FR production, as compared with hyperoxia, implying more severe myocyte injury. Based on the results of the present study, it can be concluded that O2 breathing for 24 h or higher resulted in variety of pathological changes of the endothelium of coronary capillary that were induced by the buildup of oxidants by-products. Because dobutamine caused relative higher in FR production levels, as compared with hyperoxia levels, throughout this implied it aggravated the myocyte capillaries' endothelium more heavily, which could have resulted in more intense ultrastructural deteriorations.