Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
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Introduction: The link between the elevation of the arterial blood pressure and the production of vascular lesions remains one of the most elusive issues in arterial hypertension research. Recent evidence in the spontaneously hypertensive rat and the salt dependent Dahl hypertensive strains indicate that there is an excessive production of superoxide anion in microvascular endothelium and in circulating leukocytes. The current studies were designed to examine the role of the endothelial xanthine oxidase as a source for the oxidative stress in the SHR and Dahl forms of hypertension and their normotensive controls. Materials & Methods: The oxidative stress in mesentery microcirculation SHR and Dahl (salt sensitive/resistant with and without 6% NaCl supplementation) were examined with hydroethidine and tetranitroblue tetrazolium, respectively, which form visible products upon reaction with superoxide anion. The xanthine oxidase and xanthine dehydrogenase (XD and XO) activity was measured and blocked by tungsten supplementation as well as by blockade with BOF 4272 (in the case of the SHR). Results: Both models of hypertension exhibit significantly elevated levels of XD and XO and enhanced oxidative stress in both the arterial and venular segments of the microcirculation compared with their respective normotensive controls. The elevation of the oxidative stress and blood pressures can be reduced significantly by blockade of XD and XO. Conclusions: The elevated levels of oxidative stress in the hypertensives may serve a dual role, to enhance on one hand the arteriolar tone and thus elevated central blood pressure and on the other hand to mediate the formation of proinflammatory response with lesion formation. Supported by NIH Grants HL 10881, HL 48676, and DK 43785.

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Presentation Number SAswei0837
Keywords: xanthine oxidase, hypertension, oxygen radicals, endothelium, microcirculation