Toll-Like Receptor 3 Inhibition Reduces Vasoconstriction and Blood Pressure in Spontaneously Hypertensive Rats via COX-1 Downregulation

BACKGROUND: Toll-like receptors (TLRs) are implicated in blood pressure (BP) regulation, but the role of TLR3 in hypertension remains poorly understood. We hypothesized that anti-TLR3 treatment reduces vasoconstriction and lowers BP in hypertension. METHODS: To test this, spontaneously hypertensive rats (SHR) and normotensive Wistar controls were treated with either IgG or an anti-TLR3 antibody. BP was measured, and mesenteric arteries were assessed for vascular reactivity, protein expression, and histology. RESULTS: Anti-TLR3 treatment significantly reduced BP in SHR. It also decreased the contractile response to noradrenaline, an effect abolished by indomethacin, and prevented the increased COX-1 expression in SHR while reducing COX-2 expression in both strains. Furthermore, anti-TLR3 reduced collagen I and increased collagen III deposition in the mesenteric artery and lowered TLR3 expression in the tunica media of SHR. CONCLUSION: These findings support TLR3 may represent a novel therapeutic target in hypertension.