Interaction between endothelin and angiotensin II

1. Angiotensin II (AngII) and endothelin (ET) stimulate cardiac hypertrophy in vitro and in vivo. Also AngII stimulates ET production. 2. In order to investigate whether AngII produces its cardiac hypertrophic effects through stimulating ET production which acts on the ETA receptor ma le Sprague-Dawley rats (6-8 weeks of age) received an intravenous infusion of AngII at 0, 100 or 200 ng/kg per min via Alzet osmotic minipumps and jug ular venous catheters for 7 days (n = 12 per dose). Half of the rats in eac h group received the selective ETA receptor antagonist BMS 193884 25 mg/kg per orally and the other half received the vehicle daily. 3. Telemetrically measured mean arterial pressure (MAP) rose with the 200 n g/kg per min dose of AngII (P = 0.0001), The ETA receptor blockade lowered MAP in all groups (P = 0.011), Left ventricular weights increased only in t he 200 ng/kg per min AngII infusion rats (P = 0.04), There was no effect of ETA receptor blockade on left ventricular weights. 4. These results suggest that AngII causes left ventricular hypertrophy not only in association with a presser response but also when MAP was lowered with ETA blockade to control levels, suggesting a non-presser effect of Ang II on cardiac hypertrophy, Also, ET, acting via ETA receptors, does not med iate the hypertrophic effect of AngII in this model.