Korean J Physiol Pharmacol.  2015 May;19(3):257-262. 10.4196/kjpp.2015.19.3.257.

Nicotine in High Concentration Causes Contraction of Isolated Strips of Rabbit Corpus Cavernosum

• Nguyen HB
• Lee SY
• Park SH
• Han JH
• Lee MY
• Myung SC

• KMID: 1791427
• DOI: http://doi.org/10.4196/kjpp.2015.19.3.257

Abstract

It is well known that cigarette smoke can cause erectile dysfunction by affecting the penile vascular system. However, the exact effects of nicotine on the corpus cavernosum remains poorly understood. Nicotine has been reported to cause relaxation of the corpus cavernosum; it has also been reported to cause both contraction and relaxation. Therefore, high concentrations of nicotine were studied in strips from the rabbit corpus cavernosum to better understand its effects. The proximal penile corpus cavernosal strips from male rabbits weighing approximately 4 kg were used in organ bath studies. Nicotine in high concentrations (10(-5)~10(-4) M) produced dose-dependent contractions of the corpus cavernosal strips. The incubation with 10(-5) M hexamethonium (nicotinic receptor antagonist) significantly inhibited the magnitude of the nicotine associated contractions. The nicotine-induced contractions were not only significantly inhibited by pretreatment with 10(-5) M indomethacin (nonspecific cyclooxygenase inhibitor) and with 10(-6) M NS-398 (selective cyclooxygenase inhibitor), but also with 10(-6) M Y-27632 (Rho kinase inhibitor). Ozagrel (thromboxane A2 synthase inhibitor) and SQ-29548 (highly selective TP receptor antagonist) pretreatments significantly reduced the nicotine-induced contractile amplitude of the strips. High concentrations of nicotine caused contraction of isolated rabbit corpus cavernosal strips. This contraction appeared to be mediated by activation of nicotinic receptors. Rho-kinase and cyclooxygenase pathways, especially cyclooxygenase-2 and thromboxane A2, might play a pivotal role in the mechanism associated with nicotine-induced contraction of the rabbit corpus cavernosum.

Keyword

Contraction; Cyclooxygenase; Nicotine; Rabbit corpus cavernosum; Rho-kinase

MeSH Terms

Baths
Cyclooxygenase 2
Erectile Dysfunction
Hexamethonium
Humans
Indomethacin
Male
Nicotine*
Phosphotransferases
Prostaglandin-Endoperoxide Synthases
Rabbits
Receptors, Nicotinic
Receptors, Thromboxane
Relaxation
rho-Associated Kinases
Smoke
Thromboxane A2
Tobacco Products
Cyclooxygenase 2
Hexamethonium
Indomethacin
Nicotine
Phosphotransferases
Prostaglandin-Endoperoxide Synthases
Receptors, Nicotinic
Receptors, Thromboxane
Smoke
Thromboxane A2
rho-Associated Kinases

Figure

• 

  Fig. 1 Effect of nicotine on corpus cavernous strips. High-nicotine concentrations were associated with contraction of the rabbit corpus cavernosal strips (n=12). The typical recording of these results is representative of five independent experiments (A), and the contraction was expressed in grams (g). W/O=washout (B). Each point indicates the mean±standard error of means (S.E.M.).

• 

  Fig. 2 Effect of hexamethonium (10-5 M) on nicotine-induced contractions. Hexamethonium almost completely inhibited the nicotine-induced contractions. Data are shown as the mean±standard error of means (S.E.M.) (n=12, *p<0.05). For the statistical analysis, repeated measures analysis of variance (repeated measures ANOVA) was used to evaluate differences and a *p<0.05 was considered significant.

• 

  Fig. 3 Influence of Y-27632 on the corpus cavernosal strips response to nicotine. Y-27632 (10-6 M) pretreatment markedly reduced the nicotine effects on the study strips. Data are shown as the mean±standard error of means (S.E.M.) (n=12, *p<0.05). For the statistical analysis, repeated measures analysis of variance (repeated measures ANOVA) was used to evaluate differences and a *p<0.05 was considered significant.

• 

  Fig. 4 Comparison of the effects of indomethacin (10-5 M) and NS-398 (10-6 M), nonselective COX and COX-2 inhibitors, on nicotine-induced contraction. Compared with the control, indomethacin (10-5 M) and NS-398 (10-6 M) significantly caused inhibition of the nicotine effects; however, NS-398 (10-6 M) effect might be more potent than indomethacin. Data are reported as the mean±standard error of means (S.E.M.) (n=12, *p<0.05). For the statistical analysis, repeated measures analysis of variance (repeated measures ANOVA) was used to evaluate differences and a *p<0.05 was considered significant.

• 

  Fig. 5 Effects of SQ-29548 (10-7 M) on nicotine-induced contractions. SQ-29548 pretreatment almost completely reduced nicotine-induced contractions. Data are shown as the mean±standard error of means (S.E.M.) (n=12, *p<0.05). For the statistical analysis, repeated measures analysis of variance (repeated measures ANOVA) was used to evaluate differences and a *p<0.05 was considered significant.

• 

  Fig. 6 The influence of ozagrel on the nicotine effects at a concentration of 10-5 M. Ozagrel pretreatment significantly reduced nicotine-induced contractions. Data are reported as the mean±standard error of means (S.E.M.) (n=12, *p<0.05). For the statistical analysis, the Student t-test was used to evaluate differences and a *p<0.05 was considered significant.

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