Abstract
Endothelin, a potent vasoconstrictor, is produced by cardiac fibroblasts in culture and induces hypertrophy in cardiac myoctes. The purpose of this study was to determine whether vasoactive factors endogenous to the heart affect the production of endothelin by cultured cardiac fibroblasts. Vasoactive factors have been shown to play multiple roles in the adaptation of the heart to chronic overload, affecting both vascular tone and cell growth. Both atrial (ANP) and brain (BNP) natriuretic peptides are endogenous cardiac vasodilators and are produced by cultured myocytes in response to stimulation with endothelin. Treatment of cardiac fibroblasts with these peptides decreased endothelin production. Nitroprusside, an activator of guanylyl cyclase, decreased endothelin production indicating the involvement of cGMP in the response. Carbaprostacyclin, a stable derivative of prostacyclin, another endogenous cardiac vasodilator, also decreased endothelin production by fibroblasts. The combination of BNP and carbaprostacyclin was additive in decreasing endothelin production. In contrast, PGF2α and angiotensin II, both endogenous cardiac vasoconstrictors, increased endothelin production and overcame the inhibition induced by BNP and carba-prostacyclin. In summary, endothelin production by cardiac fibroblasts was decreased by the endogenous cardiac vasodilators ANP, BNP, and prostacyclin and increased by the endogenous vasoconstrictors PGF2α and angiotensin II.
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Arai, H., Nakao, Y., Saito, N., Sugawara, T., Yamada, H., Itoh, S., Shiono, M., Mukoyama, H., Ohkubo, H., Nakanishi, S., and Imura, H. (1988).Circ. Res. 62, 926–930.
Baker, K. M., Booz, G. W., and Dostal, D. E. (1992).Annu. Rev. Physiol. 54, 227–241.
Campbell-Boswell, M., and Robertson Jr., A. L. (1981).Exp. Mol. Pathol. 35, 265–276.
Cao, L., and Gardner, D. G. (1995).Hypertension 25, 227–234.
Cho, M. J., and Allen, M. A. (1978).Prostaglandins 15, 943–954.
Crabos, M., Roth, M., Hahn, A. W. A., and Erne, P. (1994).J. Clin. Invest. 93, 2372–2378.
Csepli, J., and Csapo, A. I. (1975).Prostaglandins 10, 689–697.
De Deckere, E. A. M., Nugteren, D. H., and Ten Hoor, F. (1977).Nature 268, 160–163.
Dostal, D. E., Rothblum, K. C., Chernin, M. I., Cooper, G. R., and Baker, K. M. (1992).Am. J. Physiol. 263, C838-C850.
Dzau, V. J., and Gibbons, G. H. (1991).Hypertension 18(suppl. III), III115-III121.
Emori, T., Hirata, Y., Imai, T., Eguchi, S., Kanno, K., and Marumo, F. (1993).Endocrinology 133, 2474–2480.
Fujisaki, H., Ito, H., Hirata, Y., Tanaka, M., Hata, M., Lin, M., Adachi, S., Akimoto, F., Marumo, F., and Hiroe, M. (1995).J. Clin. Invest. 96, 1059–1065.
Gardner, D. G., and Schultz, H. D. (1990).J. Clin. Invest. 86, 52–59.
Garg, U. C., and Hassid, A. (1989).J. Clin. Invest. 83, 1774–1777.
Geisterfer, A. A. T., Peach, M. J., and Owens, G. K. (1988).Circ. Res. 62, 749–756.
Gibbons, G. H., Pratt, R. E., and Dzau, V. J. (1992).J. Clin. Invest. 90, 456–461.
Horio, T., Kohno, M., and Takeda, T. (1993).Metabolism 42, 94–96.
Hu, R. M., Levin, E. R., Pedram, A., and Frank, H. J. L. (1992).J. Biol. Chem. 267, 17,384–17,389.
Ito, H., Hirata, Y., Hiroe, M., Tsujino, M., Adachi, S., Takamoto, T., Nitta, M., Taniguchi, K., and Marumo, F. (1991).Circ. Res. 69, 209–215.
Ito, H., Hiroe, M., Hirata, Y., Fujisaki, H., Adachi, S., Akimoto, H., Ohta, Y., and Marumo, F. (1994).Circulation 89, 2198–2203.
Itoh, H., Pratt, R. E., and Dzau, V. J. (1990).J. Clin. Invest. 86, 1690–1697.
Iwaki, K., Sukhatme, V. P., Shubieta, H. E., and Chien, K. R. (1990).J. Biol. Chem. 265, 13,809–13,817.
Kalsner, S. (1975).Can. J. Physiol. Pharmacol. 53, 560–565.
Karmazyn, M., Leung, C. K. H., and Dhalla, N. S. (1979).Can. J. Physiol. Pharmacol. 57, 1275–1282.
Karmazyn, M., and Dhalla, N. S. (1983).Can. J. Physiol. Pharmacol. 61, 1207–1225.
Kim, N. N., Villarreal, F. J., Printz, M. P., Lee, A. A., and Dillman, W. H. (1995).Am. J. Physiol. 269, E426-E437.
King, K. L., Lai, J., Winer, J., Luis, E., Yen, R., Hooley, J., Williams, M., and Mather, J. P. (1996).Endocrine,5, this issue.
Kohno, M., Yasunari, K., Yokokawa, K., Murakawa, K., Horio, T., and Takeda, T. (1991).J. Clin. Invest. 87, 1999–2004.
Kohno, M., Horio T., Ikeda, M., Yokokawa, K., Fukui, T., Yasunari, K., Kurihara, N., and Takeda, T. (1992).Kidney Internat. 42, 860–866.
Kohno, M., Horio, T., Ikeda, M., Yokokawa, K., Fukui, T., Yasunari, K., Murakawa, K., Kurihara, N., and Takeda, T. (1993).Am. J. Physiol. 264, F678-F683.
Kohno, M., Ikeda, M., Johchi, M., Horio, T., Yasunari, K., Kurihara, N., and Takeda, T. (1992)Am. J. Physiol. 265, E673-E679.
Kohno, M., Yokohawa, K., Mandal, A. K., Horio, T., Yasunari, K., and Takeda, T. (1995).Metabolism 44, 404–409.
Koller, K. J., Lowe, D. G., Bennett, G. L., Minamino, N., Kangawa, K., Matsuo, H., and Goeddel D. V. (1991).Science 252, 120–123.
Lai, J., Winer, J., Yen, R., Li, W., King, K. L., Jin, H., Yang, R., Ko, A., Zeigler, F., Cheng, J., Bunting, S., Paoni, N. F. (1996).Am. J. Physiol. in press.
Lin, X., Hänze, J., Heese, F., Sodman, R., and Lang, R. E. (1995).Circ. Res. 77, 750–758.
Linssen, M. C. J. G., Engels, W., Lemmens, P. J. M. R., Heijnen, V. V. T., Bilson, M. V., Reneman, R. S., and van der Vusse, G. J. (1993).Am. J. Physiol. 264, H973-H982.
Long, C. S., Henrich, C. J., and Simpson, P. C., (1991).Cell Reg. 2, 1081–1095.
Nag, A. C. (1980).Cytobios 28, 41–61.
Nowak, J., Kaijser, A., and Wennmalm, A. (1980).Prostaglandins Med. 4, 205–214.
Ogawa, Y., Nakao, K., Mukoyama, M., Hosoda, K., Shirakami, G. Arai, H., Saito, Y., Suga, S., Jougasaki, M., and Imura, H. (1991).Circ. Res. 69, 491–500.
Ogletree, M. L., Smith, J. B., and Lefer, A. M. (1978).Am. J. Physiol. 235, H400-H406.
Prins, B. A., Hu, R. M., Nazzario, B., Pedram, A., Frank, H. J., Weber, M. A., and Levin, E. R. (1994).J. Biol. Chem. 269, 11,938–11,944.
Roberts, P. E., Phillips, D. M., and Mather, J. P. (1990).Am. J. Physiol. Lung Cell. Mol. Physiol. 3, 415–425.
Rodemann, H. P. and Goldberg, A. L. (1982).J. Biol. Chem. 257, 1632–1638.
Sadoshima, J. and Izumo, S. (1993).Circ. Res. 73, 413–423.
Saijonmaa, O., Ristimäki, A., and Fyhrquist, F., (1990).Biochem. Biophys. Res. Commun. 173, 514–520.
Sawa, H., Tokuchi, F., Mochizuki, N., Endo, Y., Furuta, Y., Shinohara, T., Takada, A., Kawaguchi, H., Yasuda, H., and Nagashima, K. (1992).Circulation 86, 138–146.
Scarborough, R. M., Hsu, M. A., Kang, L.-L., McEnroe, G. A., Schwartz, K., Arfsten, A., and Lewicki, J. A. (1989). inProgress in Atrial Peptide Research, vol. III (Brenner, B. M. and Laragh, J. H.) (eds.), Raven: New York. pp. 23–29.
Schorb, W., Booz, G. W., Dostal, D. E., Conrad, K. M., Chang, K. C., and Baker, K. M. (1993).Circ. Res. 72, 1245–1254.
Shubieta, H. E., McDonough, P. M., Harris, A. N., Knowlton, K. U., Glembotski, C. C., Brown, J. H., and Chien, K. R. (1990).J. Biol. Chem. 265, 20,555–20,562.
Smith, R. H., Palmer, R. M., and Reeds, P. J. (1983).Biochem. J. 214, 153–161.
SOLVD Investigators. (1991).N. Engl. J. Med. 325, 293–302.
Sudoh, T., Kangawa, K., Minamino, N., and Matsuo, H. (1988).Nature 332, 78–81.
Suga, S., Nakao, K., Itoh, H., Komatsu, Y., Ogawa, Y., Hama, N., and Imura, H. (1992).J. Clin. Invest. 90, 1145–1149.
Suzuki, T., Hoshi, H., Sasaki, H., and Mitsui, Y. (1991).J. Cardiovasc. Pharmacol. 17(Suppl. 7), S182-S186.
Villareal, F. J., Kim, N. N., Ungab, G. D., Printz, M. P., and Dillman, W. H. (1993).Circulation 88, 2849–2861.
Wei, C-M., Lerman, A., Rodeheffer, R. J., McGregor, C. G. A., Brandt, R. R., Wright, S., Heublein, D. M., Kao, P. C., Edwards, W. D., and Burnett, J. C. (1994).Circulation 89, 1580–1586.
Wennmalm, A. (1982). In:Prostaglandins and the Cardiovascular System (Oates, J. A.) (ed.). Raven: New York, pp. 303–331.
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King, K.L., Winer, J. & Mather, J.P. Endogenous cardiac vasoactive factors modulate endothelin production by cardiac fibroblasts in culture. Endocr 5, 95–102 (1996). https://doi.org/10.1007/BF02738661
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DOI: https://doi.org/10.1007/BF02738661