The effects of vasodilating drugs on pH in tumors

Hydralazine has been used widely to reduce tumor blood flow and thereby to induce hypoxia and to reduce extracellular pH (pHe) in tumors. Here we have investigated and compared the effects of the vasodilating drugs hydralazin e, captopril, nifedipine, prazosin, sodium nitroprusside, and labetalol to reduce pHe in EMT-6 and KHT tumors of mice and to cause antitumor effects. After a single injection, captopril was most effective in reducing pHe in E MT-6 tumors with a decrease in mean pHe from 6.93 to 6.67 at 2 h after inje ction, while nifedipine was most effective for KHT tumors with a decrease i n mean pHe from 6.96 to 6.75 at 1 h after injection. During 72 h of chronic administration into mice bearing tumors, nifedipine was ineffective in red ucing pHe, but both captopril and hydralazine caused a small but significan t reduction of pHe. Captopril caused significant delay in growth of the tum ors, but had only a small effect on clonogenic cell survival. Captopril app ears to be the most effective vasodilating drug to enhance tumor acidity.