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Comparison of effects of angiotensin peptides in the regulation of clitoral cavernosum smooth muscle tone

Abstract

The isometric tension measurement and in vitro autoradiography were used in clitoral cavernosum smooth muscle (CSM). Angiotensin ANG III, ANG IV, ANG II and ANG I induced contractions in clitoral CSM strips. ANG III and ANG I- induced contraction was five times less active than ANG II, whereas ANG IV-induced contraction was 1181-fold less potent than ANG II. Contractile responses to ANG III, ANG IV, ANG II and ANG I were significantly inhibited by type 1 ANG II (AT 1) receptor antagonist Dup 753 but not by type 2 ANG II (AT2) receptor antagonist PD 123,319. Pre-treatment with Nω-nitro-L-arginine methyl ester, nitric oxide (NO) synthase inhibitor accentuated force of contraction induced by ANG III, ANG IV and ANG II. Amastatin, an aminopeptidase inhibitor enhanced ANG III- and ANG IV-induced contractions. Specific binding sites for 125I-ANG II were found in the clitoral CSM. Specific binding of 125I-ANG II was displaced by unlabeled ANG peptides. This study suggests that the contractile responses to all four peptides of the ANG family are mediated via AT1 receptors but not AT2 receptors. Further, the rank order of potency of contraction was as follows, ANG II> ANG I>ANG III>ANG IV. It is also suggested that peptides of the ANG family have a cross-talk with the NO system and aminopeptidase is involved in the modulation of the tone of clitoral CSM by ANG III and ANG IV.

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References

  1. Timmermans PB et al . Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev 1993 45: 205–251.

    CAS  PubMed  Google Scholar 

  2. Harding JW et al . Cerebroventricular and intravascular metabolism of [125I]angiotensins in rat. J Neurochem 1986 46: 1292–1297.

    Article  CAS  PubMed  Google Scholar 

  3. Ahmad S, Ward PE. . Role of aminopeptidase activity in the regulation of the pressor activity of circulating angiotensins. J Pharmacol Exp Ther 1990 252: 643–650.

    CAS  PubMed  Google Scholar 

  4. Park JK et al . Renin angiotensin system in rabbit corpus cavernosum: functional characterization of angiotensin II receptors. J Urol 1997 158: 653–658.

    Article  CAS  PubMed  Google Scholar 

  5. Park SC, Cho KW, Park JK. . Role of renin angiotensin system in clitoral cavernosum smooth muscle. Kor J Urol 2000 42: 387–394.

    Google Scholar 

  6. Park JK et al . Renin angiotensin system of rabbit clitoral cavernosum: interaction with nitric oxide. J Urol 2000 164: 556–561.

    Article  CAS  PubMed  Google Scholar 

  7. Pendleton RG, Gessner G, Horner E. . Comparative effects of antiotensin II and angiotensin III in rabbit adrenal and aortic tissues. J Pharmacol Exp Ther 1991 256: 291–297.

    Google Scholar 

  8. Zhang QLJ, Pfaffendorf M, Van Zwieten PA. . Comparative effects of angiotensin II and its degradation products angiotensin III and angiotensin IV in rat aorta. Br J Pharmacol 1995 116: 2963–2970.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Swanson GN et al . Discovery of a distinct binding site for angiotensin II (3–8), a putative angiotensin IV receptor. Regul Pept 1992 40: 409–419.

    Article  CAS  PubMed  Google Scholar 

  10. Haberl RL, Decker PJ, Einhaupl KM. . Angiotensin degradation products mediate endothelium-dependent dilation of rabbit brain arterioles. Circ Res 1991 68: 1621–1627.

    Article  CAS  PubMed  Google Scholar 

  11. Baker KM, Aceto JF. . Angiotensin II stimulation of protein synthesis and cell growth in chick heart cells. Am J Physiol 1990 259: H610–H618.

    CAS  PubMed  Google Scholar 

  12. Campbell DJ, Kladis A, Valentijn AJ. . Effects of losartan on angiotensin and bradykinin peptides and angiotensin-converting enzyme. J Cardiovasc Pharmacol 1995 26: 233–240.

    Article  CAS  PubMed  Google Scholar 

  13. Laumann EO, Paik A, Rosen RC. . Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999 281: 537–544.

    Article  CAS  PubMed  Google Scholar 

  14. Goldstein I, Berman JR. . Vasculogenic female sexual dysfunction: vaginal engorgement and clitoral erectile insufficiency syndromes. Int J Impot of Res 1998 10: Suppl 2 S84–S90.

    Google Scholar 

  15. Munson PJ, Rodbard D. . LIGAND: a versatile computerized approach for characterization of ligand binding system. Anal Biochem 1980 107: 220–239.

    Article  CAS  PubMed  Google Scholar 

  16. Comiter CV et al . Effect of angiotensin II on corpus cavernosum smooth muscle in relation to nitric oxide environment: in vitro studies in canines. Int J Impot Res 1997 9: 135–147.

    Article  CAS  PubMed  Google Scholar 

  17. Chappel MC et al . Identification of angiotensin-(1–7) in rat brain. Evidence for differential processing of angiotensin peptides. J Biol Chem 1989 264: 16518–16523.

    Google Scholar 

  18. Cohen RB, Webb ML, Dickinson KEJ. . Peptidases and smooth muscle cell angiotensin II receptor pharmacology. Peptides 1993 14: 345–352.

    Article  CAS  PubMed  Google Scholar 

  19. Wright JW, Harding JW. . Important roles for angiotensin III and IV in the brain renin–anigotensin system. Brain Res Rev 1997 25: 96–124.

    Article  CAS  PubMed  Google Scholar 

  20. Nossaman BD et al . Analysis of responses to ANG IV: effects of PD-123319 and DuP-753 in the pulmonary circulation of the rat. Am J Physiol 1995 268: L302–L308.

    CAS  PubMed  Google Scholar 

  21. Feenstra QLM et al . Comparative vasoconstrictor effects of angiotensin II, III, and IV in human isolated saphenous vein. J Cardiovasc Pharmacol 1997 29: 451–456.

    Article  PubMed  Google Scholar 

  22. Cheng DY et al . Analysis of responses to angiotensin IV in the pulmonary vascular bed of the cat. Eur J Pharmacol 1994 261: 223–227.

    Article  CAS  PubMed  Google Scholar 

  23. Park JK, Cho KW. . Effects of angiotensin III in rabbit corpus cavernosum smooth muscle contraction: comparing with angiotensin I and angiotensin II. Kor J Urol 1999 40: 1219–1224.

    Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the Korea Health 21 Research and Development Project, Ministry of Health and Welfare, Republic of Korea (HMP-00-B-21400-0053), Korea Research Foundation (2000-041-F00239) and Alumni Association of Chonbuk National University Medical School.

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Park, J., Kim, S., Kim, J. et al. Comparison of effects of angiotensin peptides in the regulation of clitoral cavernosum smooth muscle tone. Int J Impot Res 14, 72–80 (2002). https://doi.org/10.1038/sj.ijir.3900824

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