In the DOCA-salt model, hypertension is thought to rely on brain RAS activation.41 To what degree this truly occurs is controversial, given the absence of renin in the brain.33 Indeed, the small amounts of renin that could be detected in the brain (representing blood-derived, trapped renin) disappeared after DOCA-salt treatment, in parallel with the reductions in circulating renin after this treatment. Here, REN is linked to hypertensive disorder.