Immediate hypersensitivity elicits renin release from cardiac mast cells.
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 beta-hexosaminidase release and associated with renin and norepinephrine release. Mast cell stabilization with cromolyn or lodoxamide markedly attenuated the release of beta-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.
Kano
Seiichiro
S
Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA.
Tyler
Eleanor
E
Salazar-Rodriguez
Mariselis
M
Estephan
Rima
R
Mackins
Christina J
CJ
Veerappan
Arul
A
Reid
Alicia C
AC
Silver
Randi B
RB
Levi
Roberto
R
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology*; D004205:Cromolyn Sodium / Q000494:pharmacology; D006168:Guinea Pigs; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology* / Q000502:physiology; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D009638:Norepinephrine / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012083:Renin / Q000276:immunology*; D013844:Thiazoles / Q000494:pharmacology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism; D000092502:Renin Inhibitors
D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; D004205:Cromolyn Sodium; D009638:Norepinephrine; D010047:Ovalbumin; D010072:Oxamic Acid; D011725:Pyridines; D012083:Renin; D013844:Thiazoles; D001619:beta-N-Acetylhexosaminidases; D000092502:Renin Inhibitors; C099058:BILA 2157 BS; C021702:lodoxamide ethyl