Modulation by nitric oxide of platelet-activating factor-induced albumin extravasation in the conscious rat.
1. The objective of this study was to assess whether or not endogenous nitric oxide (NO) could mediate the hypotensive response to platelet-activating factor (PAF) and modulate PAF-induced microvascular albumin leakage in the conscious rat. 2. PAF (0.19 and 1.9 nmol kg-1, i.v.) evoked dose-dependent hypotension and significantly enhanced albumin extravasation in the large airways, pancreas, stomach and duodenum 15 min after its administration. Inhibition of NO synthesis by NG-nitro-L-arginine methyl ester (L-NAME, 0.125-2 mg kg-1, i.v.) produced marked dose-dependent increases in albumin accumulation (up to 290%) in large airways, liver, spleen, pancreas, kidney, stomach and duodenum as measured by the extravasation of Evans blue dye. L-NAME (2 mg kg-1) treatment markedly potentiated PAF (1.9 nmol kg-1)-induced albumin extravasation in these tissues, whereas it did not modify the hypotensive response to PAF. 3. Maintenance of mean arterial blood pressure at the level observed following 2 mg kg-1 L-NAME by infusion of noradrenaline (620-790 ng kg-1 min-1) neither affected significantly albumin extravasation nor potentiated the permeability effect of PAF in the vascular beds studied with the exception of large airways, where noradrenaline mimicked the effects of L-NAME. 4. These results indicate that inhibition of endogenous NO formation leads to an increase in albumin extravasation and to potentiation of the vascular permeability effect of PAF, whereas the hypotensive action of PAF seems to be independent of NO formation in the conscious rat. These data suggest an important role for NO in the regulation of albumin extravasation.
Filep
J G
JG
Maisonneuve-Rosemont Hospital, Department of Medicine, University of Montréal, Québec, Canada.
Földes-Filep
E
E
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019323:omega-N-Methylarginine
D000418:Albumins; D010972:Platelet Activating Factor; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester