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Vol. 146, No. 1, 2008
Issue release date: April 2008
Int Arch Allergy Immunol 2008;146:71–75

Immediate Hypersensitivity Elicits Renin Release from Cardiac Mast Cells

Kano S. · Tyler E. · Salazar-Rodriguez M. · Estephan R. · Mackins C.J. · Veerappan A. · Reid A.C. · Silver R.B. · Levi R.
Departments of aPharmacology and bPhysiology and Biophysics, Weill Cornell Medical College, New York, N.Y., USA

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Background: We recently reported that murine and cavian heart mast cells are a unique extrarenal source of renin. Ischemia/reperfusion releases this renin leading to local angiotensin formation and norepinephrine release. As mast cells are a primary target of hypersensitivity, we assessed whether anaphylactic mast cell degranulation also results in renin and norepinephrine release. Methods: Hearts isolated from presensitized guinea pigs were challenged with antigen. Results: Cardiac anaphylaxis was characterized by mast cell degranulation, evidenced by β-hexosaminidase release and associated with renin and norepinephrine release. Mast cell stabilization with cromolyn or lodoxamide markedly attenuated the release of β-hexosaminidase, renin and norepinephrine. Renin inhibition with BILA2157 did not affect mast cell degranulation, but attenuated norepinephrine release. Conclusions: Our findings disclose that immediate-type hypersensitivity elicits renin release from mast cells, activating a local renin-angiotensin system, thereby promoting norepinephrine release. As renin is stored in human heart mast cells, allergic reactions could initiate renin release, leading to local angiotensin formation and hyperadrenergic dysfunction.

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