It is hypothesized that the renin–angiotensin system, involved in hypertension and in the central nervous system (CNS), could at least partially be responsible for the association between migraine and hypertension9,22 This in turn, might be the explanation to the observations that some angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARB) are shown to be effective in preventing migraine attacks as well as beta-blockers suppressing cortical excitability (cortical spreading depression).22–25. This evidence concerns the gene REN and hypertensive disorder.