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Role of rho-kinase activity in angiotensin II-induced contraction of rabbit clitoral cavernosum smooth muscle

Abstract

Isometric tension measurement using a selective Rho-kinase inhibitor (+)- (R)-trans4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide (Y-27632) and a selective myosin light chain kinase (MLCK) inhibitor 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML7) were used in rabbit clitoral cavernosum smooth muscle (CSM). NG-nitro-L-arginine methyl ester (L-NAME) was used to evaluate the relationship between NO release and Rho-kinase. Y-27632 significantly attenuated contractions induced by ANG II, dose-dependently. However, ML7 did not affect the contractile response to ANG II except in the high concentrations of ML7. Y-27632 inhibited contraction with phenylephrine (PhE), but ML7 did not inhibit contraction with PhE. Nitric oxide synthase inhibitor (NAME) did not affect the Y-27632-induced relaxation in the pre-contracted strip with PhE. The present study demonstrates that G-protein-coupled increase in myofilament Ca2+ sensitivity mediated through the RhoA/Rho-kinase signal pathway is involved in the control by ANG II of the clitoral CSM tone. RhoA/Rho-kinase pathway acts in the ANG II-induced contraction independently of the NO pathway.

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References

  1. Timmermans PB et al. Angiotension II receptor subtypes Am J Hypertens 1992; 5: 406–410.

    Article  CAS  PubMed  Google Scholar 

  2. 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 

  3. 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 

  4. Kifor I et al. Tissue angiotensin II as a modulator of erectile function. I. Angiotensin peptide content, secretion and effects in the corpus cavernosum J Urol 1997; 157: 1920–1925.

    Article  CAS  PubMed  Google Scholar 

  5. Leiblum SR, Baume RM, Croog SH . The sexual functioning of elderly hypertensive women J Sex Marital Ther 1994; 20: 250–270.

    Article  Google Scholar 

  6. Somlyo AP, Somlyo AV . Signal transduction and regulation in smooth muscle Nature 1994; 372: 231–236.

    Article  CAS  PubMed  Google Scholar 

  7. Kitazawa T, Masuo M, Somlyo AP . G protein-mediated inhibition of myosin light-chain phosphatase in vascular smooth muscle Proc Natl Acad Sci 1991; 88: 9307–9310.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nakahara T et al. Y-27632 potentiates relaxant effects of beta 2-adrenoceptor agonists in bovine tracheal smooth muscle Eur J Pharmac 2000; 389: 103–106.

    Article  CAS  Google Scholar 

  9. Chitaley K et al. Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway Nat Med 2001; 7: 119–122.

    Article  CAS  PubMed  Google Scholar 

  10. Kimura K et al. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase) Science 1996; 273: 245–248.

    Article  CAS  PubMed  Google Scholar 

  11. Boivin D, Bilodeau D, Beliveau R . Regulation of cytoskeletal functions by Rho small GTP-binding proteins in normal and cancer cells Can J Physiol Pharmac 1996; 74: 801–810.

    Article  CAS  Google Scholar 

  12. Takaishi K et al. Translocation of activated Rho from the cytoplasm to membrane ruffling area, cell-cell adhesion sites and cleavage furrows Oncogene 1995; 11: 39–48.

    CAS  PubMed  Google Scholar 

  13. Karnam P et al. Activation and translocation of Rho (and ADP ribosylation factor) by insulin in rat adipocytes. Apparent involvement of phosphatidylinositol 3-kinase J Biol Chem 1997; 272: 6136–6140.

    Article  CAS  PubMed  Google Scholar 

  14. Uehata M et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension Nature 1997; 389: 990–994.

    Article  CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  16. Kureishi Y et al. Rho-associated kinase directly induces smooth muscle contraction through myosin light chain phosphorylation J Biol Chem 1997; 272: 12257–12260.

    Article  CAS  PubMed  Google Scholar 

  17. Navar LG et al. Paracrine regulation of the renal microcirculation Physiol Rev 1996; 76: 425–536.

    Article  CAS  PubMed  Google Scholar 

  18. Freeman EJ, Tallant EA . Vascular smooth-muscle cells contain AT1 angiotensin receptors coupled to phospholipase D activation Biochem J 1994; 304: 543–548.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yamakawa T et al. Involvement of Rho-kinase in angiotensin II-induced hypertrophy of rat vascular smooth muscle cells Hypertension 2000; 35: 313–319.

    Article  CAS  PubMed  Google Scholar 

  20. Fu X et al. The effects of the Rho-kinase inhibitor Y-27632 on arachidonic acid-, GTPgammaS-, and phorbol ester-induced Ca2+-sensitization of smooth muscle FEBS Lett 1998; 440: 183–187.

    Article  CAS  PubMed  Google Scholar 

  21. Cellek S, Moncada S . Nitrergic control of peripheral sympathetic responses in the human corpus cavernosum: a comparison with other species Proc Natl Acad Sci USA 1997; 94: 8226–8231.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Chitaley K, Webb RC . Nitric oxide induces dilation of rat aorta via inhibition of Rho-kinase signaling Hypertension 2002; 39: 438–442.

    Article  CAS  PubMed  Google Scholar 

  23. Mills TM, Chitaley K, Lewis RW, Webb RC . Nitric oxide inhibits RhoA/Rho-kinase signaling to cause penile erection Eur J Pharmac 2002; 439: 173–174.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by a grant from the Institute of Clinical Medicine of Chonbuk National University Hospital.

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Correspondence to J K Park.

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Park, J., Lee, S., Kim, Y. et al. Role of rho-kinase activity in angiotensin II-induced contraction of rabbit clitoral cavernosum smooth muscle. Int J Impot Res 14, 472–477 (2002). https://doi.org/10.1038/sj.ijir.3900911

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