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 (*O(-)(2)) and nitric oxide anion (*NO(-)), are highly toxic and have detrimental effects on nitroso-redox balance in the myocyte. Myocardium is rich with beta-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% O(2)) 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% O(2) breathing) for 24,48, and 72 h, whereas the 5th, 6th, and 7th groups were injected dobutamine 10,20, and 30 microg 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.

Vascular Degeneration in Parkinson's Disease

“…Using 10 mm as a cutoff line for measuring the capillaries (<10 mm) and small arteries/ veins (>10 mm), we found that the PD cases had fewer capillaries (in the RN) and more small arterioles/veins (in the LC) with a significant reduction in the ratio of small/large vessels throughout all nuclei. The data suggest that vessel degeneration in PD cases was primarily at the level of capillaries, which may themselves be more vulnerable to degeneration than the small arteries/veins, and/or to the enlarged capillaries as a result of vascular remodeling (27). The transformation of the microvasculature from predominantly capillaries to predominantly small arterioles/venules has a profound effect on oxygen diffusion.…”

Effects of oxygen, growth state, and senescence on the antioxidant responses of WI-38 fibroblasts

“…A widely held view is that oxygen toxicity arises from increased oxygen free radical generation in cells (Beckman and Ames 1998; Mattar and Haffor 2009), and it has been observed that exposure to hyperoxia accelerates the accumulation of oxidative by-products such as lipofuscin (von Zglinicki et al 1995), which would seem to support the hypothesis.…”

Statins and Cognition in Parkinson’s Disease

“…Simvastatin reduces mitochondrial stress in myocytes [50], yet effects on neurons is unknown. Statins may contribute to cognitive reserve in PD by reducing ROS in the medial frontal gyrus/cortex, an area found to exhibit increased vascular burden in PD [49].…”