Although aspirin and other NSAIDs are commonly perceived as harmless, they may be dangerous for hypertensive patients. We recently showed that in hypertensive mice, genetic suppression of the renal vessel EP4 receptor (which mimics downstream effects of NSAIDs) leads to a massive reduction in renal perfusion. However, direct genetic manipulation of a drug end target is not the same thing as actually administering the drug. Thus, we repeated that study, this time giving aspirin instead of using genetic manipulation. Hypertensive rats that drank aspirin water suffered severe kidney damage and 2/5 died. For hypertensive patients, NSAIDs warrant extreme caution.