Plasminogen Activator Inhibitor-1 Antagonist TM5441 Attenuates N ^ω -Nitro- <scp>l</scp> -Arginine Methyl Ester–Induced Hypertension and Vascular Senescence

Abstract

Pharmacological inhibition of PAI-1 is protective against the development of hypertension, cardiac hypertrophy, and periaortic fibrosis in mice treated with L-NAME. Furthermore, PAI-1 inhibition attenuates the arterial expression of p16(Ink4a) and maintains telomere length. PAI-1 appears to play a pivotal role in vascular senescence, and these findings suggest that PAI-1 antagonists may provide a novel approach in preventing vascular aging and hypertension.