Abstract 550: Large Blood Pressure Variability Aggravates Arteriolosclerosis and Ischemic Changes in the Kidney in Hypertensive Rats

Abstract

Background: Increased blood pressure (BP) variability (BPV) is a characteristic feature of hypertensive patients. Large BPV aggravates hypertensive target organ damage, such as left ventricular hypertrophy, carotid atherosclerosis, and microalbuminuria. We have shown that angiotensin II (AngII)-mediated inflammation plays a role in the aggravation of hypertensive cardiac remodeling in spontaneously hypertensive rats (SHR) with large BPV. However, little was known regarding renal damages induced by large BPV. The aims of this study were to investigate pathological changes of the kidney and to examine whether candesartan would prevent the renal damages in SHR with large BPV. Methods and Results: A model of a combination of hypertension and large BPV was created by bilateral sino-aortic denervation (SAD) in SHR at 12 weeks old. SAD increased BPV without changes in mean BP. At 19 weeks old, SAD induced patchy cortical interstitial lesions associated with ischemic changes of glomeruli and tubules and interstitial fibrosis. The interlobular or afferent arterioles around ischemic lesions showed remarkable arteriolosclerotic changes characterized by vascular smooth muscle cell proliferation and extracellular matrix deposition, leading to the luminal narrowing and occlusion (Figure). Chronic treatment with a subdepressor dose of candesartan prevented not only arteriolosclerotic changes but also interstitial fibrosis and ischemic changes in SHR with SAD. Conclusion: Large BPV aggravates renal arteriolosclerosis, which results in the cortical ischemic changes and fibrosis in the kidney of hypertensive rats through angII-mediated mechanisms.