TLR4 and hypertensive disorder: In this context, we argue that (a) if the mechanism by which systemic TLR4 blockade lowers BP in diabetic animals involves suppression of the RAS system, in animals receiving exogenous AngII, the treatment would not impact BP; (b) blockade of TLR4 reduces vascular contractility in small resistance arteries10, which directly contributes to BP regulation by modifying total peripheral resistance33; and, (c) although diabetes and hypertension have many overlapping mechanisms, they are independent diseases.