This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features!
Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log in
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jul;82(1):253.e17-24.
doi: 10.1016/j.urology.201304009.

Analysis of erectile responses to imatinib in the rat

Affiliations

Analysis of erectile responses to imatinib in the rat

Edward A Pankey et al. Urology. 2013 Jul.

Abstract

Objective: To investigate the erectile and cardiovascular responses to the tyrosine kinase inhibitor imatinib in the rat.

Materials and methods: The effect of intracavernosal injection of imatinib on the intracavernosal pressure (ICP), ICP/mean arterial pressure (MAP) ratio, area under the curve, and duration of the increase in ICP and the effect of intravenous injection of imatinib on the MAP, cardiac output, and total peripheral resistance were investigated. The effect of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester on the responses to imatinib was investigated.

Results: Intracavernosal injection of imatinib produced significant dose-related increases in the ICP, ICP/MAP ratio, area under the curve, and duration of the increase in ICP and decreases in the MAP. The erectile responses to imatinib were rapid in onset and short in duration. The erectile responses to imatinib were not significantly altered by NG-nitro-L-arginine methyl ester or cavernosal nerve crush injury, and imatinib was significantly less potent than the nitric oxide donor sodium nitroprusside in inducing erection. Intravenous injection of imatinib produced significant dose-related decreases in the MAP without significantly changing the cardiac output, and imatinib was significantly less potent than sodium nitroprusside in decreasing the MAP. Systemic vascular resistance was decreased in a significant dose-related manner, and the vasodilator responses to imatinib were not altered by NG-nitro-L-arginine methyl ester.

Conclusion: The present results have indicated that imatinib has significant erectile and systemic vasodilator activity in the rat that is not dependent on nitric oxide release. Another tyrosine kinase inhibitor, nilotinib, also increased the ICP and decreased the MAP in the rat. These data suggest that tyrosine kinases might play a constitutive role in maintaining penile tumescence and the baseline vasoconstrictor tone in the peripheral vascular bed.

PubMed Disclaimer

Figures

Figure 1
Figure 1
(A) Bar graph showing peak change in intracavernosal pressure and changes in intracavernosal pressure/mean systemic arterial pressure ratio (ICP/MAP), area under curve (AUC), and duration in response to intracavernosal injection of imatinib 0.1–10.0 mg/kg. (B) Bar graph showing decrease in MAP in response to intracavernosal (ic) injection of imatinib in doses of 0.1–10 mg/kg. (C) Bar graph showing changes in ICP/MAP ratio in response to intracavernosal (ic) injection of nilotinib 1–10 mg/kg. Line graphs showing time course of (D) increase in ICP and (E) decrease in MAP in response to intracavernosal injection of imatinib 10 mg/kg. n, number of rats. *P <.05, analysis of variance.
Figure 2
Figure 2
(A) Bar graphs showing effect of nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) 50 mg/kg intravenously on increase in intracavernosal pressure (ICP) in response to cavernosal nerve stimulation at 16 Hz, increase in ICP/mean systemic arterial pressure (MAP) ratio in response to intracavernosal (ic) injection of imatinib 0.3–10.0 mg/kg, and total erectile response (area under curve [AUC]) induced by intracavernosal injection of imatinib 0.3–10.0 mg/kg. (B) Bar graphs showing effects of cavernosal nerve crush injury on increase in ICP in response to cavernosal nerve stimulation at 16 Hz, increase in ICP/MAP ratio in response to intracavernosal injection of imatinib 10 mg/kg, and total erectile response (area under curve [AUC]) induced by intracavernosal injection of imatinib 10 mg/kg. n, number of experiments. *P <.05, paired comparison.
Figure 3
Figure 3
Bar graphs showing effect of intravenous (iv) injections of imatinib 0.3–30.0 mg/kg on change in mean arterial pressure, change in cardiac output, and percentage of change in systemic vascular resistance (SVR) (A) under control conditions and (B) after treatment with nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (50 mg/kg iv). n, number of experiments. *P <.05, analysis of variance.
Figure 4
Figure 4
Line graphs comparing dose-response curves for (A) intracavernosal (ic) injections of sodium nitroprusside (SNP) (1, 3, and 10 μg/kg) and imatinib (1, 3, and 10 mg/kg) on changes in intracavernosal pressure and (B) intravenous (iv) injections of SNP (1, 3, and 10 μg/kg) and imatinib (1, 3, and 10 mg/kg) on changes in mean systemic arterial pressure. n, number of experiments.

References

    1. Hubbard SR, Miller WT. Receptor tyrosine kinases: mechanisms of activation and signaling. Curr Opin Cell Biol. 2007;19:117–123. - PMC - PubMed
    1. Schiffer CA. BCR-ABL tyrosine kinase inhibitors for chronic myelogenous leukemia. N Engl J Med. 2007;357:258–265. - PubMed
    1. Min Y, He P, Wang Q, et al. The effects of the c-kit blocker Glivec on the contractile response of urinary bladder. J Surg Res. 2011;171:e193–e199. - PubMed
    1. Kubota Y, Biers SM, Kohri K, et al. Effects of imatinib mesylate (Glivec) as a c-kit tyrosine kinase inhibitor in the guinea-pig urinary bladder. Neurourol Urodyn. 2006;25:205–210. - PubMed
    1. Ozgur-Akdemir A, Demirturk K, Karabakan M, et al. Imatinib mesylate (Gleevec) as protein-tyrosine kinase inhibitor elicits smooth muscle relaxation in isolated human prostatic tissue. Urology. 2011;78:968e1–968.e6. - PubMed

MeSH terms

LinkOut - more resources

Full text links
Elsevier Science full text link Elsevier Science Free PMC article
Cite

AltStyle によって変換されたページ (->オリジナル) /