Abstract 231: Hydrogen Sulfide Promotes Macrophage Polarization to Reduce Renal Inflammation in Angiotensin-II Induced Hypertension

Abstract

Ageing is associated with structural and functional changes in the kidney and the presence of hypertension in this population further contributes to renal complications leading to renovascular sclerosis. Emerging evidence suggests that hydrogen sulfide (H 2 S) pathway participates in the pathogenesis of hypertension. Furthermore, chronic inflammation is known to play a critical role in ageing and development of hypertension. In this study, we hypothesized that angiotensin-II (Ang-II)-induced hypertension causes renal fibrosis by sustained activation of pro-inflammatory M1 macrophage promoting the release of inflammatory cytokines and treatment with H 2 S attenuates renal injury and fibrosis by promoting alternate activation of anti-inflammatory M2 macrophage. C57BL/6J (wild type, WT) mice, aged 18 months, were infused with Ang-II (1000ng/Kg/min) or saline using osmotic pumps for 4 weeks and treated without or with H 2 S in drinking water (30μM/L). Animal groups were 1) Saline, 2) Saline + H 2 S, 3) Ang-II, 4) Ang-II + H 2 S. Blood pressure was measured weekly and renal ultrasound was done to measure hemodynamic parameters. Systolic and diastolic blood pressure was increased in mice receiving Ang-II (160.73 ± 4.5 and 129.10 ± 4.9 respectively) and treatment with H 2 S showed significant reduction (134.5 ± 4.8 and 101.1 ± 4.5 respectively). Ultrasound revealed increased renal artery and intra-renal cortical artery resistive index in Ang-II mice (0.73 ± 0.03) which was significantly decreased following H2S treatment (0.61 ± 0.2). Ang-II increased the protein expression and mRNA levels of pro-inflammatory M1 macrophage marker, CD40, and TNF-α and MCP-1, whereas, H2S treatment increased the expression of anti-inflammatory M2 macrophage marker, CD206, and IL-10. Fluorescent probe H2DCF-DA showed increased intracellular reactive oxygen species with Ang-II treatment which was abrogated with H2S treatment. Our data suggests that H 2 S treatment in Ang-II-induced hypertension attenuates inflammation and hypertension by reducing classical activation of inflammatory M1 macrophage and promotes alternate activation of anti-inflammatory M2 macrophage.