Abstract 179: Blood Pressure Variability-Induced Aggravation of End-Organ Damages Is Another Achievable Target of Hypertension Treatment. -Effects of Angiotensin Receptor Blocker on an Animal Model-
Background: An increase in blood pressure (BP) variability (BPV) is seen with aging and hypertension. Hypertensive patients with large BPV have aggravated end-organ damages and increased cardiovascular risk. However, the pathogenesis has remained unknown. Recently, we have shown that pressure overload induces angiotensin II (angII)-mediated perivascular inflammation and reactive fibrosis in rat heart. We assessed the hypothesis that large BPV aggravates hypertensive myocardial remodeling and cardiac dysfunction by activating inflammatory process and angII-mediated system.
Methods and Results: A rat model of chronic hypertension with large BPP was created by performing bilateral sinoaortic denervation (SAD) in spontaneous hypertensive rats (SHR) at 12 weeks old (w). At 19 w, SAD exaggerated BPV without changing mean BP in SHR. SAD enhanced myocyte hypertrophy and myocardial fibrosis by 1.4-fold and 4-fold, respectively, accompanied by a reduction in LV fractional shortening. SAD induced myocardial macrophage infiltration and inductions of IL-1β, MCP-1, TGF-β, angiotensinogen and angII type 1 receptor (AT1R) mRNAs. Chronic treatment with a subdepressor dose of candesartan not only prevented the SAD-induced myocyte hypertrophy and myocardial fibrosis but also reversed LV dysfunction without affecting BPV. Candesartan prevented the SAD-induced macrophage infiltration and inductions of MCP-1, TGF-β, angiotensinogen and AT1R. But, candesartan did not change the upregulation of IL-1β, an activator of angiotensinogen and AT1R expressions, suggesting that IL-1β induction may be an upperstream event of the angII-mediated inflammation induced by BPV.
Conclusion. Large BPV aggravated hypertensive myocardial remodeling and systolic dysfunction by activating myocardial inflammation. Blocking of AngII-mediated system ameliorated the BPV-induced inflammation and cardiac remodeling, even though BPV was not changed. The present study provided new insight into the understanding that BPV-induced aggravation of end-organ damages is another achievable target of hypertension treatment.