| pubmed-article:7585817 | pubmed:abstractText | Elevations in plasma angiotensin II (AngII) are associated with an efflux of plasma macromolecules into the perivascular and contiguous interstitial space. Whether this exudative response is related to associated hypertension or another effect of AngII is uncertain. We therefore monitored plasma and cardiac lymph total protein, albumin and fibronectin and calculated transvascular clearances for total protein (TVPC) and albumin (TVAC) and lymph fibronectin transport (LFT) every 30 min in open-chested, instrumented dogs. After baseline observations were obtained over 30 min, pressor (250 ng.kg.min-1) or nonpressor (11 ng.kg.min-1) doses of AngII were given intravenously for 90 min. Saline-treated, instrumented dogs served as controls. To address a potential secondary effect of AngII on vascular protein clearance, we monitored lymph prostaglandin E2 and cGMP (a marker of released nitric oxide, NO). At > or = 30 min, each dose of AngII was associated with a significant (P < or = 0.05) and comparable increase in TVPC, TVAC and LFT over baseline, indicating that increase in protein clearance was not related to elevated arterial pressure. Lymph cGMP rose significantly (P < or = 0.05) at 30 min for each dose of AngII and remained elevated thereafter. Lymph PGE2 was increased at > or = 60 min (P < or = 0.05) but only with the pressor dose. To determine the contribution of NO and PGE2 on AngII-induced transcoronary protein clearance, each dose of AngII was accompanied by co-administration of either the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), or the cyclo-oxygenase inhibitor, indomethacin. L-NAME completely inhibited the release of cGMP and the increase in protein clearance was not seen. Indomethacin suppressed the release of PGE2, but did not prevent the increase in protein clearance. Thus, AngII-induced increase in transcoronary protein clearance is not related to arterial hypertension or the release of PGE2, but instead appears to be mediated by NO release. | lld:pubmed |
