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-arginine) on plasma extravasation induced by intravenously administered substance P, [pGlu5,Me-Phe8,Sar9]substance P-(5-11) or prostaglandin E2 was examined. Control rats were more responsive than diabetic rats to both 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, but potentiated those of [pGlu5,Me-Phe8,Sar9]substance P-(5-11) in control rats. In diabetic rats N omega-nitro-L-arginine, which did not affect the actions of the substance P analogue, exerted complex effects on substance P induced plasma extravasation giving potentiation in the tongue, inhibition in bronchioles, and no effect in other tissues. N omega-Nitro-L-arginine inhibited prostaglandin E2 induced extravasation 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.
Mathison
R
R
Department of Medical Physiology, Faculty of Medicine, University of Calgary, Alberta, Canada.
Davison
J S
JS
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D015232:Dinoprostone / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010446:Peptide Fragments / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology*
D001786:Blood Glucose; D010446:Peptide Fragments; D019335:Nitroarginine; D013373:Substance P; C032720:substance P (5-11), pGlu(5)-MePhe(8)-MeGly(9)-; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D015232:Dinoprostone; D011761:Pyrrolidonecarboxylic Acid