Abstract
Two small molecular weight fibrin degradation product, the pentapeptide 6A and the undecapeptide 6D, produced relaxations of norepinephrine-contracted rabbit aorta strips. The relaxations were slow-developing and were elicited by both peptides at supramicromolar concentrations; the amplitude of relaxations were small for 6D. The relaxations induced by 6A were not dependent on the presence of endothelium and were not modified by a mixture of indomethacin, pyrilamine, and cimetidine. The amplitude of the relaxations produced by 6A and 6D increased as a function of incubation timein vitro.
In another experimental system, peptides 6A and 6D failed to increase 6-keto-PGF1α release from cultured human umbilical endothelial cells. Histamine and bradykinin were both active in this system.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
B. Gerdin and T. Saldeen,Effect of fibrin degradation products on microvascular permeability. Thromb. Res.13, 995–1006 (1978).
M. Belew, B. Gerdin, J. Porath and T. Saldeen,Isolation of vasoactive peptides from human fibrin and fibrinogen degraded by plasmin. Thromb. Res.13, 983–994 (1978).
B. Gerdin, M. Belew, O. Lindquist and T. Saldeen,Effect of a fibrin-derived peptide on pulmonary microvascular permeability. In:The microembolism syndrome. (Ed. T. Saldeen), pp. 233–239, Almqvist & Wiskell International, Stockholm 1979.
M. Belew, B. Gerdin, G. Linddeberg, J. Porath, T. Saldeen and R. Walling,Structure-activity relationships of vasoactive peptides derived from fibrin or fibrinogen degraded by plasmin. Biochim. Biophys. Acta.621, 169–178 (1980).
B. Gerdin, L. Juhlin and T. Saldeen,Cutaneous reactions to two fibrin-derived peptides. Acta Dermatovener.61, 558–560 (1981).
R. G. G. Andersson, K. Saldeen and T. Saldeen,A fibrin(ogen) derived pentapeptide induces vasodilation, prostacyclin release and an increase in cyclic AMP. Thromb. Res.30, 213–218 (1985).
J. Mehta, T. Wargovich, W. W. Nichols, K. Saldeen, R. Wallin and T. Saldeen,Peptide 6A, a fibrin(ogen) degradation product, increases coronary blood flow. Am. J. Physiol.249, H457-H462 (1985).
T. Saldeen, J. W. Ryan and P. Berryer,A peptide derived from fibrin(ogen) inhibits angiotensin converting enzyme and potentiates the effects of bradykinin. Thromb. Res.23, 465–470 (1981).
D. Regoli and J. Barabé,Pharmacology of bradykinin and related kinins. Pharmacol. Rev.32, 1–46 (1980).
T. E. Hugli and F. Marceau,Effects of the C5a anaphylatoxin and its relationship to cyclo-oxygenase metabolites in rabbit vascular strips. Br. J. Pharmacol.84, 725–733 (1985).
C. Lundberg, F. Marceau, R. Huey and T. E. Hugli,Anaphylatoxin C5a fails to promote prostacyclin release in cultured endothelial cells from human umbilical veins. Immunopharmacology12, 135–143 (1986).
R. B. Merrifield,Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J. Am. Chem. Soc.85, 2149–2154 (1963).
A. R. Mitchell, S. B. H. Kent, M. Engelgard and R. B. Merrifield,A new synthetic route to tertbutyloxycarbonylaminoacyl-4-(oxymethyl) phenylacetamidomethylresin, an improved support for solid phase peptide synthesis. J. Org. Chem.43, 2845–2852 (1978).
B. F. Gisin,Preparation of Merrifield resins through total esterification with caesium salts. Helv. Chim. Acta56, 1476–1482 (1973).
S. A. St-Pierre, J. M. Lalonde, M. Gendreau, R. Quirion, D. Regoli and F. Rioux,Synthesis of peptides by the solid-phase method. 6. Neurotensin, fragments and analogs. J. Med. Chem.24, 370–376 (1981).
W. Koenig and R. Geiger,New method for the synthesis of peptides: activation of the carbonyl group with dicyclohexylcarbodiimide by using 1-hydroxybenzotriazole as additive. Chem. Ber.103, 788–798 (1970).
E. Kaiser, R. L. Colescot, C. D. Bossinger and P. I. Cook,Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides. Anal. Biochem.34, 595–598 (1970).
R. F. Furchgott and S. Bhadrakom,Reactions of strips of rabbit aorta to epinephrine, isopropylarterenol, sodium nitrite and other drugs. J. Pharmacol. Exp. Ther.108, 129–143 (1953).
F. Marceau and T. E. Hugli,Effect of C3a and C5a anaphylatoxins on guinea pig blood vessels. J. Pharmacol. exp. Ther.230, 749–754 (1985).
R. F. Furchgott,Role of endothelium in responses of vascular smooth muscle. Circ. Res.53, 557–573 (1983).
M. Eriksson, K. Saldeen, T. Saldeen, K. Strandberg and R. Wallin,Fibrin-derived vasoactive peptides release histamine. Int. J. Microcirc. Clin. Exp.2, 337–345 (1983).
S. L. Hong,Effect of bradykinin and thrombin on prostacyclin synthesis in endothelial cells from calf and pig aorta and human umbilical cord vein. Thromb. Res.18, 787–795 (1980).
F. Alhenc-Gelas, F. S. J. Tsai, K. S. Callahan, W. B. Campbell and A. R. Johnson,Stimulation of prostaglandin formation by vasoactive mediators in cultured human endothelial cells. Prostaglandins24, 723–742 (1982).
U. Forstermann, G. Hertting and B. Neufang,The importance of endogenous prostaglandins other than prostacyclin for the modulation of contractility of some rabbit blood vessels. Br. J. Pharmacol.81, 623–630 (1984).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Marceau, F., Bouthillier, J., Tremblay, B. et al. Effects of low molecular weight fibrin degradation products 6A and 6D on rabbit aorta strips. Agents and Actions 22, 43–49 (1987). https://doi.org/10.1007/BF01968815
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01968815