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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Apr 1;90(7):2885–2889. doi: 10.1073/pnas.90.7.2885

Endothelial cells are required for the cAMP regulation of cardiac contractile proteins.

G McClellan 1, A Weisberg 1, L E Lin 1, D Rose 1, C Ramaciotti 1, S Winegrad 1
PMCID: PMC46201  PMID: 8385348

Abstract

The contractile proteins in mammalian cardiac muscle are regulated by a cAMP-dependent reaction that alters the activity of the actomyosin ATPase. The ATPase activity of cardiac actomyosin has also been shown to depend on factors released by small arteries in the myocardial tissue. Endothelial cells have been implicated in the regulation of the contractile force developed by isolated cardiac tissue. To determine whether endothelial cells are required for the cAMP-dependent regulation of the contractile proteins, the effect of cAMP on the actomyosin ATPase activity was measured in cryostatic sections of isolated, quickly frozen rat ventricular trabeculae. In half of the trabeculae, the endocardial endothelial cells had been damaged by a 1-sec exposure to 0.5% Triton X-100. In trabeculae with intact endothelial cells, cAMP increased actomyosin ATPase activity toward an apparently maximum value. In trabeculae with damaged endothelial cells, cAMP did not change actomyosin ATPase activity. The coronary venous effluent from an isolated heart has already been shown to modify the maximum isometric force developed by an isolated trabecula. The extent to which the force of the isolated trabecula is changed by the coronary venous effluent is closely related to the degree to which cAMP has up-regulated the actomyosin ATPase activity in the isolated heart donating the coronary effluent: the greater the degree of up-regulation of ATPase activity, the greater the increase in force produced by the effluent. These results indicate that endothelial cells are required for the cAMP-dependent regulation of cardiac contractile proteins to function, and these results further suggest that the myocardium autoregulates by modulating the cAMP regulation of contractile proteins with endothelial-derived factors.

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Selected References

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  1. Brutsaert D. L., Meulemans A. L., Sipido K. R., Sys S. U. Effects of damaging the endocardial surface on the mechanical performance of isolated cardiac muscle. Circ Res. 1988 Feb;62(2):358–366. doi: 10.1161/01.res.62.2.358. [DOI] [PubMed] [Google Scholar]
  2. Brutsaert D. L. The endocardium. Annu Rev Physiol. 1989;51:263–273. doi: 10.1146/annurev.ph.51.030189.001403. [DOI] [PubMed] [Google Scholar]
  3. Furchgott R. F., Vanhoutte P. M. Endothelium-derived relaxing and contracting factors. FASEB J. 1989 Jul;3(9):2007–2018. [PubMed] [Google Scholar]
  4. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  5. Ishikawa T., Yanagisawa M., Kimura S., Goto K., Masaki T. Positive inotropic action of novel vasoconstrictor peptide endothelin on guinea pig atria. Am J Physiol. 1988 Oct;255(4 Pt 2):H970–H973. doi: 10.1152/ajpheart.1988.255.4.H970. [DOI] [PubMed] [Google Scholar]
  6. Kato N. S., Weisberg A., Winegrad S. Effect of left atrial filling pressure on the activity of specific myosin isozymes in rat heart. Circ Res. 1991 Jun;68(6):1582–1590. doi: 10.1161/01.res.68.6.1582. [DOI] [PubMed] [Google Scholar]
  7. Kelly R. A., Eid H., Krämer B. K., O'Neill M., Liang B. T., Reers M., Smith T. W. Endothelin enhances the contractile responsiveness of adult rat ventricular myocytes to calcium by a pertussis toxin-sensitive pathway. J Clin Invest. 1990 Oct;86(4):1164–1171. doi: 10.1172/JCI114822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lin L. E., McClellan G., Weisberg A., Winegrad S. A physiological basis for variation in the contractile properties of isolated rat heart. J Physiol. 1991 Sep;441:73–94. doi: 10.1113/jphysiol.1991.sp018739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. McClellan G. B., Winegrad S. Cyclic nucleotide regulation of the contractile proteins in mammalian cardiac muscle. J Gen Physiol. 1980 Mar;75(3):283–295. doi: 10.1085/jgp.75.3.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. McClellan G., Weisberg A., Kato N. S., Ramaciotti C., Sharkey A., Winegrad S. Contractile proteins in myocardial cells are regulated by factor(s) released by blood vessels. Circ Res. 1992 Apr;70(4):787–803. doi: 10.1161/01.res.70.4.787. [DOI] [PubMed] [Google Scholar]
  11. Neely J. R., Liebermeister H., Battersby E. J., Morgan H. E. Effect of pressure development on oxygen consumption by isolated rat heart. Am J Physiol. 1967 Apr;212(4):804–814. doi: 10.1152/ajplegacy.1967.212.4.804. [DOI] [PubMed] [Google Scholar]
  12. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  13. Ramaciotti C., Sharkey A., McClellan G., Winegrad S. Endothelial cells regulate cardiac contractility. Proc Natl Acad Sci U S A. 1992 May 1;89(9):4033–4036. doi: 10.1073/pnas.89.9.4033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Rubanyi G. M., Vanhoutte P. M. Hypoxia releases a vasoconstrictor substance from the canine vascular endothelium. J Physiol. 1985 Jul;364:45–56. doi: 10.1113/jphysiol.1985.sp015728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Smith J. A., Shah A. M., Lewis M. J. Factors released from endocardium of the ferret and pig modulate myocardial contraction. J Physiol. 1991 Aug;439:1–14. doi: 10.1113/jphysiol.1991.sp018653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Winegrad S., McClellan G., Horowits R., Tucker M., Lin L. E., Weisberg A. Regulation of cardiac contractile proteins by phosphorylation. Fed Proc. 1983 Jan;42(1):39–44. [PubMed] [Google Scholar]
  17. Winegrad S., Weisberg A., Lin L. E., McClellan G. Adrenergic regulation of myosin adenosine triphosphatase activity. Circ Res. 1986 Jan;58(1):83–95. doi: 10.1161/01.res.58.1.83. [DOI] [PubMed] [Google Scholar]
  18. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411–415. doi: 10.1038/332411a0. [DOI] [PubMed] [Google Scholar]
  19. Yoshizumi M., Kurihara H., Sugiyama T., Takaku F., Yanagisawa M., Masaki T., Yazaki Y. Hemodynamic shear stress stimulates endothelin production by cultured endothelial cells. Biochem Biophys Res Commun. 1989 Jun 15;161(2):859–864. doi: 10.1016/0006-291x(89)92679-x. [DOI] [PubMed] [Google Scholar]

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