L-arginine and NG-nitro-L-arginine methyl ester cause macromolecule extravasation in the microcirculation of awake hamsters.
We investigated the effects of L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) on macromolecule extravasation in the microcirculation of awake hamsters by computer-assisted image analysis of the distribution of FITC (fluorescein isothiocyanate)-dextran fluorescence in dorsal fold skin preparations. This analysis made it possible to simultaneously study the time course of local (skin) and general (all irrigated organs) extravasation in 180-min experiments. Bolus injection of 30 or 150 mg/kg (i.v.) L-arginine induced immediate local and general macromolecule leakage and delayed venule dilation beginning 1 h later. Injection of 20 or 100 mg/kg (i.v.) L-NAME caused rapid venule constriction followed by local and general extravasation beginning 45-60 min later. These effects of L-arginine and L-NAME were not mimicked by their biologically inactive isomers, D-arginine and D-NAME. Simultaneous bolus injection of 20 mg/kg L-NAME and 150 mg/kg L-arginine caused no significant change in fluorescence distribution or venule diameter. L-arginine effects on macromolecule extravasation were mimicked by sodium nitroprusside (10 microg/kg, i.v.) and by 8-bromo-cGMP (1 mg/kg, i.v.). Sodium nitroprusside was ineffective on venule diameter. The effects of both L-arginine and sodium nitroprusside on FITC-dextran extravasation were prevented by simultaneous injection (10 microg/kg, i.v.) of the specific inhibitor of the soluble guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). This dose of ODQ mimicked the effects of L-NAME on macromolecule extravasation and venule diameter. Taken together, these results suggest that activation or inhibition of basal NO synthesis might induce macromolecule leakage in the microcirculation of awake hamsters via temporally distinct cGMP-dependent mechanisms.
Gimeno
G
G
Pharmacology Department, Laboratoire INNOTHERA, Arcueil, France.
Carpentier
P H
PH
Desquand-Billiald
S
S
Hanf
R
R
Finet
M
M
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D014699:Venules / Q000033:anatomy & histology
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase