Comparison of the Effects of Intravenously Bolus‐administered Endothelin‐1 and Infused Angiotensin II on the Subcutaneous Tumor Blood Flow in Anesthetized Rats

To evaluate the effects of endothelin‐1 (ET‐1) on tumor blood flow, the authors measured the mean arterial blood pressure (MABP) of enflurane‐anesthetized male Donryu rats and the tissue blood flow of subcutaneously implanted tumor (Yoshida rat ascites hepatoma LY‐80) by using a hydrogen clearance method. The tumor blood flow was evaluated in terms of the ratio to the maximum blood flow, which was defined as the largest flow in the same position during successive measurements. After bolus intravenous administration of ET‐1 (1.0 nmol/kg), MABP reached approximately 140 mmHg (at 5 30 min), diminishing gradually to the baseline level over 2 h. The tumor blood flow increased from 36.7 ± 20.6 to 59.5 ± 30.2% (n = 32, P <0.001, at 2 min), returning to the baseline level at 10 min. On the other hand, at 2 min after the beginning of continuous intravenous infusion of [Asp(1), Ile(5)]‐angiotensin II (AII; the dose was determined by a blood pressure control system for keeping MABP at approximately 150 mmHg, consequently 0.26 μg/kg/min on the average), the tumor blood flow increased from 42.3 ±21.6 to 76.4±22.6% (n = 32, P < 0.001), which was significantly larger than the flow after ET‐1. The results indicate that hypertension induced by systemic ET‐1 injection is less effective than hypertension induced by continuous systemic AII infusion in increasing tumor blood flow; AII is probably a suitable agent as a safe and effective enhancer of tumor blood flow. Moreover, ET‐1 appears to constrict arterial vessels in the microcirculation time‐dependently, while AII constricts probably only normal peripheral arterioles.