Pulmonary Anaphylaxis and the Kallikrein-Kinin System
The kallikrein-kinin system has been thought to participate in the pathogenesis of anaphylaxis. Kallikrein, released from lungs, has been postulated to contribute to cardiovascular collapse. Further to test the hypothesis, we examined for the occurrence of a kallikrein-like enzyme in guinea pig lungs and. examined for release of such an enzyme by isolated, perfused lungs of guinea pig sensitized to and challenged with egg albumin. In addition, we treated guinea pigs with the bradykinin potentiating agents, BPP9a and SQ 14,225. In parallel experiments, we examined for effects of non-steroidal anti-inflammatory agents on the supposition that prostaglandin-related substances may mediate or modulate actions of kinins during anaphylaxis. A plasma kallikrein-like enzyme was found in lung homogenates and occurred in concentrations greater than that of plasma itself. Similarly, a store of kininogen occurs in lungs. However, using a sensitive radioassay for kallikrein-like enzymes, we were unable to confirm that antigenic challenge of sensitized lungs causes the release of enzyme into pulmonary venous effluent. Further, we were unable to modify the acute course of anaphylaxis by pretreatment of guinea pigs with bradykinin potentiating agents. However, indomethacin and aspirin at 20–40 mg/kg were found to greatly increase the severity of pulmonary anaphylaxis in terms of increased resistance to ventilation and increased numbers of lung hemorrhages. Paradoxically, aspirin or sodium salicylate at 80–100 mg/kg prevents the characteristic rise of insufflation pressure and the formation of lung hemorrhages.
KeywordsPerfuse Lung Sodium Salicylate Antigenic Challenge Lung Homogenate Insufflation Pressure
Unable to display preview. Download preview PDF.
- Amundsen, E., L. Svendsen, A.M. Venner$id and K. Laake, Determination of plasma kallikrein with a new chromogen.ic tripeptide derivative, 1976 In: Chemistry and Biology of the Kallikrein-Kinin System in Health and Disease. Fogarty Int. Center Proc. No 27, eds. J.J. Pisano and K.F. Austen (U.S. Government Printing Office, Washington ) p. 215.Google Scholar
- Brocklehurst, W.E. and S.C. Lahíri, 1962. The production of bradykinin in anaphylaxis, J. Physiol., 160: 15.Google Scholar
- Brocklehurst, W.E. and S.C. Lahiri, 1963. Formation and destruction of bradykinin during anaphylaxis. J. Physiol., 165: 39.Google Scholar
- Chung, A.C., J.W. Ryan, G. Pena and N.B. Oza. (this volume), A simple radioassay for human urinary kallikrein.Google Scholar
- Collier, H.O.J. Role of the kallikrein-kinin system in lung diseases, 1976 In: Chemistry and Biology of the KallikreinKinin System in Health and Disease. Fogarty Int. Center Proc. No. 27, eds. J.J. Pisano and K.F. Austen (U.S. Government Printing Office, Washington ) p. 495.Google Scholar
- Engineer, D.M., U. Niederhauser, P.J. Piper and P. Sirois, 1978. Release of mediators of anaphylaxis: Inhibition of prostaglandin synthesis and the modification of release of slow reacting substances on anaphylaxis and histamine. Br. J. Pharmac. 62: 61.Google Scholar
- Levi, R., G. Allan and J.H. Zavecz, 1976. Cardiac histamine receptors. Fed. Proc., 35: 1942.Google Scholar
- Newball, H.H., S.D. Revak, C.G. Cochrane, J.H. Griffin and L.M. Lichtenstein, 1978. Cleavage of hageman factor (HF) by a basophil kallikrein of anaphylaxis (BK-A). Clin. Res., 26: 519A.Google Scholar
- Newball, H.H., R.C. Talamo and L.M. Lichtenstein, 1975. Release of leukocyte kallikrein mediated by IgE, Nature 254: 635Google Scholar
- Rocha e Silva, M., W.T. Beraldo and G. Rosenfeld, 1949. Bradykinin, a hypotensive and smooth muscle stimulating factor released from plasma by snake venoms and by trypsin. Am. J. Physiol., 156: 261.Google Scholar
- Ryan, J.W., A. Chung, L.C. Martin and U.S. Ryan, 1978. New substrates for the radioassay of angiotensin converting enzyme of endothelial cells in culture. Tissue & Cell. 10: 555.Google Scholar
- Ryan, J.W., J. Roblero and J.M. Stewart, 1968. Inactivation of bradykinin in the pulmonary circulation. Biochem. J., 110: 795.Google Scholar