Browsing by Author "Govender, Melvin M."

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Oxidative stress of tissue in hypertensive rats.
(2006) Govender, Melvin M.; Nadar, Anand.
Oxidative stress, resulting from an antioxidant/free radical imbalance, is considered to be an important etiologic factor in the patho-physiological changes associated with salt sensitive hypertension. An important unresolved issue in hypertension research is the mechanism for organ damage during the development of the syndrome. Reactive oxygen species (ROS) such as the superoxide radical (02) , hydrogen peroxide (H202), and the hydroxyl radical (OH), may playa critical role in the pathogenesis of hypertension by targeting the very tissue that is responsible for regulating blood pressure, during the hypertensive state. Thus, this study was undertaken to evaluate the antioxidant and free radical status in the DSS rat strain, which has been shown to be an excellent model of salt sensitive hypertension. The antioxidant status was evaluated on the basis of the vascular superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, and the free radical status was evaluated on the basis of the plasma H20 2 concentration. The levels of malonyldialdehyde (MDA), which is a bio-marker for lipid peroxidation was used to determine the level of oxidative stress in the kidney, liver and brain. The kidney and liver were also subjected to an induced free radical mediated lipid peroxidation, by exposing the tissue to increasing known concentrations of H202 (2.5mM - 15mM). The level of lipid peroxidation was used to assess the tissues antioxidant buffering capacity to an induced free radical "attack". The results have shown that the DSS strain may have a compensatory increase in vascular SOD levels, to counter an increase in 02-. SOD levels were significantly lower during salt loading. The GPx levels were significantly lower in the DSS strain, and showed a slight increase during salt loading. The results demonstrate that the DSS strain has a compromised antioxidant status compared to the DSR strain. The plasma H202concentration displayed non-significant changes in the DSS strain, however salt loading did result in a non-significant increase in the plasma H202 concentration in the DSS strain. The GPx : HZ02 ratio, demonstrated an inadequate increase in GPx levels during salt loading to neutralise this non-significant increase in HzOz concentration. The kidney showed an increased level of in vivo lipid peroxidation, which could implicate increased tissue damage, and thus confirm the kidney as being a target organ during the hypertensive state. The liver and brain showed non-significant differences in the level of in vivo lipid peroxidation and are therefore thought not to be target tissue in the hypertensive state. The kidney displayed a decreased antioxidant buffering capacity to the induced free radical "attack", thereby demonstrating the tissue's decreased ability to neutralise an increased free radical level. Although the liver displayed a "normal" level of in vivo lipid peroxidation, it also displayed a decreased antioxidant buffering capacity to an induced free radical "attack", showing that the liver is able to cope with in vivo free radical levels, but at higher free radical levels, its loses its ability to quench a free radical "attack" and thereby minimise lipid peroxidation. The in vivo lipid peroxidation levels of the kidney, liver and brain have shown that tissues have varying abilities to cope with tissue oxidative stress, and behave differently, in their free radical quenching abilities. These results have shown that a compromised free radical and antioxidant status results in oxidative damage to the tissue responsible for regulating blood pressure.
The role of angiotensin ll and oxidative stress in the spontaneously hypertensive rat.
(2011) Govender, Melvin M.; Nadar, Anand.
Oxidative stress resulting from an imbalance between free radicals and antioxidants is considered to be an important etiological factor in the development and maintenance of hypertension. Angiotensin II (Ang II) has been shown to be an important regulator of blood pressure and acts to elevate blood pressure by its pressor effects. The pressor effects of Ang II are well documented but recent evidence has suggested another possible role of Ang II in elevating blood pressure, whereby it acts via an independent mechanism that is directly linked with oxidative stress. The spontaneously hypertensive rat (SHR) is a widely used model in the investigation of the pathophysiological mechanisms involved in hypertension. This study was therefore undertaken to determine whether Ang II acts as a causative factor via oxidative stress in the development and maintenance of hypertension in the SHR. This was elucidated by evaluating the role of both the endogenous in vivo levels of Ang II as well as an exogenous sub-pressor dose of Ang II, on oxidative stress and its associated parameters. The parameters evaluated included, the antioxidant status of the model on the basis of the levels of the major antioxidant enzymes viz. SOD, GPx and catalase; the free radical generating capacity, by assessing the activity of the membrane bound enzyme NADPH oxidase and the levels of H2O2. The study also evaluated the levels of the endogenous vasodilator nitric oxide (NO), remodelling of the vasculature and the level of tissue oxidative stress in the kidney. The results show that the SHR has an elevated plasma Ang II level and an elevated level of oxidative stress, thus showing that in this model there is an intimate link between oxidative stress and Ang II. The SHR also shows depleted levels of NO and thus a decreased vasodilatory capacity and increased remodelling of the vasculature. The kidney showed an increased level of lipid peroxidation, which was due to the elevated levels of oxidative stress. All of these pathophysiological changes contribute to the elevation in blood pressure in this model. The long term infusion of the sub-pressor dose of Ang II affected the SHR to a greater extent than the Wistar. Although the dose of Ang II elevated the blood pressure in both models, the degree of the pathophysiological changes associated with the elevation in blood pressure was greater in the SHR. The Ang II infusion in both these models demonstrated that in the SHR which is genetically predisposed to hypertension, adjustments are made to the antioxidant system, that result in an elevated level of protection against oxidative stress. These results show that Ang II acts as a causative factor in the pathogenesis of hypertension in the SHR via its well documented pressor effects, as well as via a multitude of independent mechanisms that are linked to oxidative stress. This is substantiated by the significant decrease in NO that is caused by the elevated oxidative stress, as well as the previously described pathophysiological changes. This study has therefore shown that Ang II has an intimate causative link with oxidative stress that results in parallel mechanisms that work concomitantly with each other in hypertension in this model.