ALTERED VASCULAR-PERMEABILITY RESPONSES TO SUBSTANCE-P IN DIABETIC RATS - INTERACTIONS WITH A NITRIC-OXIDE SYNTHESIS INHIBITOR

The effect of inhibiting nitric oxide synthase (N(omega)-nitro-L-argin ine) on plasma extravasation induced by intravenously administered sub stance P, [pGlu5,Me-Phe8,Sar9]substance P-(5-11) or prostaglandin E2 w as examined. Control rats were more responsive than diabetic rats to b oth substance P and [pGlu5,Me-Phe8,Sar9]-substance P-(5-11). N(omega)- Nitro-L-arginine blocked the actions of substance P on dorsal skin, bu t potentiated those of [pGlu5,Me-Phe8,Sar9]substance P-(5-11) in contr ol rats. In diabetic rats N(omega)-nitro-L-arginine, which did not aff ect the actions of the substance P analogue, exerted complex effects o n substance P induced plasma extravasation giving potentiation in the tongue, inhibition in bronchioles, and no effect in other tissues. N(o mega)-Nitro-L-arginine inhibited prostaglandin E2 induced extravasatio n in control, but not diabetic rats. The altered plasma extravasation in diabetic rats may be due to diabetes induced alterations in nitric oxide synthesis or in the responses of the endothelial cells to nitric oxide.