Abstract 783: Exaggerated Blood Pressure Variability Aggravates Hypertensive Cardiac Remodeling through the Angiotensin II-Mediated Inflammation in Rats
Background: Hypertensive patients with large blood pressure (BP) variability have greater risks of cardiovascular events and exaggerated end-organ damages. Recently, we have shown that acute pressure overload triggers transient perivascular inflammation.
Hypothesis: We assessed the hypothesis that large BP variability exaggerates hypertensive cardiac remodeling through the activation of myocardial inflammation.
Methods and Results: A new rat model of chronic hypertension with exaggerated BP variability was created by performing bilateral sino-aortic denervation (SAD) in spontaneous hypertensive rats (SHRs). Seven weeks after SAD (n=10) or sham (n=7) operation (week 7), 24-hour BP was monitored telemetrically in SAD+SHRs and sham+SHRs. Although mean BP was similar in the two groups, SAD+SHRs had greater BP variability (larger standard deviation and covariance of mean BP), compared with sham+SHRs. Both the two groups showed concentric left ventricular (LV) hypertrophy, and SAD aggravated LV hypertrophy by 1.3-fold. SAD+SHRs had histologically greater myocyte hypertrophy and myocardial fibrosis by 1.4-fold and 4.7-fold, respectively, relative to sham+SHRs. Perivascular macrophage infiltration was evident in SAD+SHRs, but not in sham+SHRs. SAD remarkably upregulated expressions of myocardial angiotensinogen and monocyte chemoattractant protein-1 (MCP-1). To determine the role of angiotensin II in the BP variability-induced cardiac remodeling, non-depressor dose of angiotensin II receptor blocker, candesartan, was orally given to SHRs everyday from 1 week after SAD (n=7). At week 7, the small dose of candesartan attenuated LV and myocyte hypertrophy and myocardial fibrosis in SAD+SHRs without changing BP and BP variablility. Moreover, candesartan reversed MCP-1 upregulation and macrophage accumulation in SAD+SHRs to the levels of sham+SHRs.
Conclusions: Exaggerated BP variability aggravates hypertensive cardiac hypertrophy and fibrosis through chronic activation of inflammatory process. And, angiotensin II would play a key role in the activation of the inflammatory process, independently of the presser effect.