Aging-related induction of inducible nitric oxide synthase is vasculo-protective to the arterial media

• Published in: Cardiovascular research 2004-03, Vol.61 (4), p.796-805
• Main Authors: FERRINI, Monica G, DAVILA, Hugo H, VALENTE, Eliane G. A, GONZALEZ-CADAVID, Nestor F, RAJFER, Jacob
• Format: Article
• Language: English
• Subjects: Aging - physiology; Animals; Apoptosis; Arteries; Arteriosclerosis - metabolism; Biological and medical sciences; Cardiology. Vascular system; Collagen - metabolism; Enzyme Activation; Erectile Dysfunction - metabolism; Fibrosis; Male; Medical sciences; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type II; Penis - blood supply; Plasminogen Inactivators - metabolism; Rats; Rats, Inbred BN; Reactive Oxygen Species - analysis; Reactive Oxygen Species - metabolism
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/j.cardiores.2003.12.006

Aging associated erectile dysfunction (ED) is primarily caused by the reduction in smooth muscle cells (SMC) and an increase in collagen within the corpora cavernosa, assumed to result from an increase in reactive oxygen species (ROS). This is accompanied by the expression of inducible nitric oxide synthase (iNOS) to produce nitric oxide that scavenges ROS and inhibits collagen deposition. We investigated whether with aging similar processes occur within the arterial media SMC that share some common physiological functions with the cavernosal SMC. Aged (22-24 months) male Brown Norway rats received water with or without an inhibitor of iNOS activity (L-N-(iminoethyl)-lysine acetate [L-NIL], 0.1 g/l), for 3 weeks. Young (3 months) untreated rats were used as control (n=5 per group). Tissue sections from the penis, abdominal aorta, femoral and brachial arteries were stained for collagen, SMC, iNOS, ROS plasminogen activator inhibitor (PAI) and apoptosis, and evaluated by quantitative image analysis. ROS were also determined in fresh tissue and whole blood by the GSH/GSSG ratio. It was observed that most aging-induced changes in the media of the arterial tree from the aorta to the resistance arteries in the penis are similar to what occurs in the corpora cavernosa, i.e. a decrease in the SMC/collagen ratio and an increase in ROS and iNOS, and specifically in the case of the resistance arteries, an increase in SMC apoptosis and PAI. iNOS inhibition by L-NIL further increased ROS and decreased the SMC/collagen ratio in the media. These observations suggest that ED and arteriosclerosis in the aging male may share a common etiology, and that the expression of iNOS by the SMC is an attempt to counteract this fibrosis.