Blockade of angiotensin II type-1 receptor increases salt sensitivity in Sprague–Dawley rats

Abstract

This study determined the role of angiotensin II type-1 (AT1) receptor in the salt sensitivity of blood pressure. The mean arterial blood pressure (MAP) of Sprague-Dawley rats was monitored by radio telemetry and, after baseline measurements, rats were treated either with (1) vehicle, (2) AT1 receptor blocker (ARB) olmesartan (OLM, 100 nmol kg(-1) h(-1), subcutaneously), (3) OLM with hydrochlorothiazide (HCTZ, 40 mg kg(-1) day(-1), orally), (4) angiotensin II (AngII, 100 ng kg(-1) min(-1), subcutaneously) or with (5) AngII with OLM. Rats were fed a 0.5% salt diet during the baseline and first 7 days of treatment period, and the diet was then switched to one containing 8% salt for another 7 days. Urinary samples were collected in a metabolic cage at the end of each period. MAP of the vehicle group did not change throughout the study. In AngII-infused rats, BP increased only when rats were fed an 8% salt diet. OLM and OLM with AngII significantly reduced MAP when rats were on a 0.5% salt diet, but not on an 8% salt diet, indicating an enhanced salt sensitivity by OLM. Co-treatment with HCTZ reduced the salt sensitivity of OLM. The urinary level of the oxidative stress marker was increased by an 8% salt diet and was not altered by either OLM alone or in combination with HCTZ. However, OLM attenuated the salt-induced renal NAD(P)H (nicotinamide adenine dinucleotide phosphate) oxidase activity. These results indicate that AT1 receptor blockade increases salt sensitivity, which is reversed by diuretics. We conclude that OLM and HCTZ could be a useful combination for reduction of blood pressure even under high salt intake without changes in urinary oxidative stress levels.