Effect of long-term passive smoking on erectile function and penile nitric oxide synthase in the rat

Purpose: Given that smoking is a risk factor for erectile dysfunction, this study aimed to determine, in a rat model, whether long-term exposure to cigarette smoke impairs nitric oxide (NO)-dependent erectile function and reduces penile nitric oxide synthase (NOS), and if these changes are accompanied with effects on the systemic blood pressure. Materials and Methods: Adult (5 month) and old (20 month) rats were exposed to daily passive smoking for 8 wks. Three days after the conclusion of exposure, half of the animals were submitted to electrical field stimulation (EFS) of the cavernosal nerve and the maximum intracavernosal pressure (MIP) and mean arterial pressure (MAP) were determined and expressed as mm. Hg. On the other half of the animals, NOS activity in the penile cytosol was measured by the arginine/citrulline assay, and neuronal NOS (nNOS) and endothelial NOS (eNOS) contents were estimated by western blot and densitometry. Results: When compared to controls, the smoking rats had a higher MAP in both the adult (115 vs 162) and old (113 vs 140) rats, but surprisingly the MIP also increased, from 78 to 111 (adult rats) and from 59 to 83 (old rats). Smoking reduced penile NOS activity by 73% (adult rats), and 62% (old rats), and nNOS content by 43% and 50%, respectively. In contrast, eNOS was not affected. Nitrite release, in vitro, by cavernosa slices or in rat penile smooth muscle cells (RPSMC) was not inhibited by nicotine or cotinine. Conclusion: These results indicate that chronic smoking in the rat leads to age-independent moderate hypertension and considerable decreases in penile NOS activity and nNOS content, that are not reflected in a reduction of the erectile response to EFS or accompanied by a decrease in penile eNOS.