Aortic Stiffness in L-NAME Treated C57Bl/6 Mice Displays a Shift From Early Endothelial Dysfunction to Late-Term...

Area of Science:

• Cardiovascular Aging Research
• Vascular Biology
• Pharmacology

Background:

• Endothelial dysfunction is a key indicator of cardiovascular aging.
• N-Ω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) is a standard model for inducing cardiovascular aging in small animals.
• Specific changes in aortic function during L-NAME-induced aging are not fully understood.

Purpose of the Study:

• To longitudinally characterize aortic reactivity and biomechanical changes in L-NAME treated C57Bl/6 mice.
• To investigate the temporal relationship between arterial stiffness, hypertension, and cardiac hypertrophy.
• To elucidate the underlying mechanisms of aortic dysfunction in this aging model.

Main Methods:

• Male C57Bl/6 mice received L-NAME in drinking water for up to 16 weeks.
• Measurements included blood pressure, echocardiography, aortic pulse wave velocity (aPWV), and ex vivo aortic ring function.
• Aortic stiffness was assessed using Peterson modulus (Ep), and endothelial/vascular smooth muscle cell function was evaluated through pharmacological challenges.

Main Results:

• L-NAME treatment induced progressive hypertension and cardiac hypertrophy.
• Aortic stiffening was observed early, preceding hypertension and cardiac aging, and accelerated arterial stiffening by twofold.
• Early endothelial dysfunction resolved, followed by late-term vascular smooth muscle cell dysfunction, characterized by altered calcium handling and channel activity.

Conclusions:

• Arterial stiffness is an early event in L-NAME-induced cardiovascular aging, preceding hypertension and cardiac hypertrophy.
• The study identified a distinct progression of aortic disease, shifting from initial endothelial dysfunction to later vascular smooth muscle cell dysfunction.
• These findings provide critical insights into the mechanisms of age-related vascular changes and potential therapeutic targets.