ovalbumin and lodoxamide-ethyl

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.. Hearts isolated from presensitized guinea pigs were challenged with antigen.. 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.. 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.

Topics: Animals; Anti-Allergic Agents; Anti-Asthmatic Agents; beta-N-Acetylhexosaminidases; Cell Degranulation; Cromolyn Sodium; Guinea Pigs; Hypersensitivity, Immediate; In Vitro Techniques; Male; Mast Cells; Myocardium; Norepinephrine; Ovalbumin; Oxamic Acid; Pyridines; Renin; Thiazoles

The effects of ketotifen and lodoxamide on eosinophil infiltration were assessed in a guinea pig model of allergic conjunctivitis. The two active treatments were coded in this masked study in which 30 male guinea pigs, sensitized to chicken egg albumin (ovalbumin), were randomly assigned to one of three groups: Group 1, instillation of 0.9% NaCl into the conjunctival sac of both eyes; Group 2, instillation of 0.025% ketotifen into the left eye and 0.9% NaCl into the right eye; Group 3, instillation of 0.1% lodoxamide into the left eye and 0.9% NaCl into the right eye. Ovalbumin was administered topically to each eye, except in Group 1 where it was only applied to the left eye. (111)In-oxine labeled eosinophils were injected into the jugular vein of each guinea pig; the animals were sacrificed 17 hours after ovalbumin had been applied. The level of radioactivity in the ketotifen- and lodoxamide-treated eyes was approximately 60% of that in the saline-treated eyes. Moreover, the mean level of radioactivity in the ketotifen- and lodoxamide-treated eyes was comparable with the mean level of radioactivity in the saline-treated eye of Group 1, which had not been exposed to allergen. These results indicate that the therapeutic effects of ketotifen and lodoxamide in allergic conjunctivitis may be partly mediated by an inhibitory effect on eosinophils.

Topics: Administration, Topical; Animals; Anti-Allergic Agents; Cell Movement; Conjunctivitis, Allergic; Eosinophils; Guinea Pigs; Ketotifen; Male; Ovalbumin; Oxamic Acid

Orally administered iodoxamide ethyl (U-42,718) inhibited anaphylactic reactions in a dose-related manner in the following test animals: (1) in the rat PCA reaction, excellent activity (75% inhibition at 0.1 mg/kg) was seen with a duration of activity of 30 min, (2) In the ascaris-sensitive primate (45% inhibition at 1.0 mg/kg) in lung parameters related to increased resistance and decreased compliance which persisted for up to 3 h, and (3) 50 mg/kg protected guinea pigs, sensitized to egg albumin, from lung function changes. Activity in these animal systems indicates that this orally active drug may hold promise in clinical asthma.

Topics: Aerosols; Amino Acids; Anaphylaxis; Animals; Ascaris; Female; Guinea Pigs; Haplorhini; Macaca mulatta; Male; Ovalbumin; Oxamic Acid; Passive Cutaneous Anaphylaxis; Rats; Respiration; Tidal Volume