Chronic Cigarette Smoking Impairs Erectile Function through Increased Oxidative Stress and Apoptosis, Decreased nNOS, Endothelial and Smooth Muscle Contents in a Rat Model.
Cigarette use is an independent risk factor for the development of erectile dysfunction (ED). While the association between chronic smoking and ED is well established, the fundamental mechanism(s) of cigarette-related ED are incompletely understood, partly due to no reliable animal model of smoking-induced ED. The present study was designed to validate an in vivo rat model of chronic cigarette-induced ED. Forty 12-week old male Sprague-Dawley rats were divided into 4 groups. Ten rats served as control group and were exposed only to room air. The remaining 30 rats were passively exposed to cigarette smoke (CS) for 4 weeks (n = 10), 12 weeks (n = 10), and 24 weeks (n = 10). At the 24-week time point all rats were assessed with intracavernous pressure (ICP) during cavernous nerve electrostimulation. Blood and urine were collected to measure serum testosterone and oxidative stress, respectively. Corporal tissue was assessed by Western blot for neuronal nitric oxide synthase (nNOS). Penile tissues were subjected to immunohistochemistry for endothelial, smooth muscle, and apoptotic content. Mean arterial pressure (MAP) was significantly higher in 24-week cigarette exposed animals compared to the control animals. Mean ICP/MAP ratio and cavernosal smooth muscle/endothelial contents were significantly lower in the 12- and 24-week rats compared to control animals. Oxidative stress was significantly higher in the 24-week cigarette exposed group compared to control animals. Mean nNOS expression was significantly lower, and apoptotic index significantly higher, in CS-exposed animals compared to control animals. These findings indicate that the rat model exposure to CS increases apoptosis and oxidative stress and decreases nNOS, endothelial and smooth muscle contents, and ICP in a dose dependent fashion. The rat model is a useful tool for further study of the molecular and cellular mechanisms of CS-related ED.
Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Yun-Ching
YC
Huang
Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Chih-Chien
CC
Chin
Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Chih-Shou
CS
Chen
Department of Urology, University of California Davis, Davis, CA, United States of America.
Alan W
AW
Shindel
Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Dong-Ru
DR
Ho
Knuppe Molecular Urology Laboratory, Department of Urology, University of California San Francisco, San Francisco, CA, United States of America.
Ching-Shwun
CS
Lin
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Chung-Sheng
CS
Shi
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001835:Body Weight; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004727:Endothelium / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D018384:Oxidative Stress; D010410:Penile Erection; D017207:Rats, Sprague-Dawley; D012907:Smoking; D013739:Testosterone / Q000097:blood / Q000652:urine
D013739:Testosterone; D052248:Nitric Oxide Synthase Type I