Both endothelium-dependent and -independent relaxation were compromised in TgNotch3R169C pulmonary arteries, recapitulating previous results in TgNotch3R169C cerebral arteries43 and peripheral vessels in patients with CADASIL.8 We examined eNOS signaling as the regulator of endothelial-dependent relaxation but failed to demonstrate altered activity. This evidence concerns the gene NOS3 and CADASIL.