Abstract 125: Low-Grade Chronic Infection Induces Vascular Dysfunction and Remodeling in Salt Sensitive Hypertension

Abstract

According to the new AHA guidelines, over half of Americans have hypertension. Multiple factors contribute to hypertension including genetics, diet, stress, and infection. N-formyl peptides (NFPs) are a potent chemoattractant that bind formyl peptide receptors (FPR), an innate immune receptor. Interestingly, the only source of NFPs are bacteria and mitochondria, which evolved from bacteria. We have observed that FPR is expressed in arteries and its activation with bacterial (fMLPs) or mitochondrial (FMIT) NFPs induces vascular remodeling via actin polymerization. Given that increased gut permeability is present in hypertension, we questioned if bacterial NFPs derived from a leaky gut also play a role in hypertension. We hypothesized that bacterial NFPs activate FPR leading to vascular dysfunction and remodeling. We used male (6 weeks) Dahl Resistant (DR) and Sensitive (DS) rats on a low (0.3 %) or high salt (2 %) diet for 9 weeks. After 6 weeks some animals on high salt received water + antibiotic [neomycin (NEO), 0.5 g/L or amoxicillin (AMO), 50 mg/kg/day) for 3 weeks to decrease bacterial levels. Statistics: t-test *p<0.05. We observed that FPR mRNA expression was increased in aorta from DS (low-salt) when compared to DR (low-salt) (DR: 0.96 ± 0.7 vs. DS: 1.3 ± 1.7*), suggesting that FPR is activated prior to the onset of hypertension. High-salt diet increased FPR mRNA expression in aorta from DR, but did not exacerbate it in DS compared to DS (low-salt). Phenylephrine and acetylcholine concentration-response curves (1nM – 1μM) were performed in mesenteric resistance arteries using wire myography. Due to increased arterial stiffness from severe hypertension in DS (high salt), these rats showed a decrease in contraction compared to DR. DS treated with NEO or AMO ameliorated this response (tension (mN): Emax: DS 11 ± 4 vs. DS+ NEO 17 ± 2*, S + AMO 17 ± 0.9*). No changes were observed in the relaxation curve. Using pressure myograph, it was observed that NEO and AMO reverted vascular remodeling [wall thickness (μm): DS 55 ± 4 vs. DS + NEO 38 ± 9* and DS + AMO 31± 9*; cross sectional area (μm 2 ): DS 45,624 ± 1370 vs. DS + NEO 28,700 ± 8370* and DS + AMO 23,276 ± 9775*]. We concluded that low-grade chronic infection plays a role in vascular dysfunction and remodeling observed in hypertension.