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 ET(A) receptor, male 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 jugular venous catheters for 7 days (n = 12 per dose). Half of the rats in each group received the selective ET(A) 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 ng/kg per min dose of AngII (P = 0.0001). The ET(A) receptor blockade lowered MAP in all groups (P = 0.011). Left ventricular weights increased only in the 200 ng/kg per min AngII infusion rats (P = 0.04). There was no effect of ET(A) receptor blockade on left ventricular weights. 4. These results suggest that AngII causes left ventricular hypertrophy not only in association with a pressor response but also when MAP was lowered with ET(A) blockade to control levels, suggesting a non-pressor effect of AngII on cardiac hypertrophy. Also, ET, acting via ET(A) receptors, does not mediate the hypertrophic effect of AngII in this model.