title: Similar permeability responses to nitric oxide synthase inhibitors of venules from three animal species.
abstract: The influence of nitric oxide (NO) on microvascular permeability remains unclear. NO synthase (NOS) inhibitors have been reported to increase as well as to decrease permeability in different experimental models and animal species. We tested the hypothesis that NOS inhibitors influence venular permeability differently in amphibians and mammals. Permeability coefficients to albumin (P(alb)(s)) were measured on in situ mesenteric venules of the frog and rat and excised pig coronary venules before and after exposure to NOS inhibitors. Despite individual variability in magnitude of responses, NOS inhibitors resulted in a reduction in P(alb)(s) in each species. Superfusion with 10(-5) M N(G)-monomethyl-l-arginine (l-NMMA) reduced P(alb)(s) of frog mesenteric venules by 42% (from a median of 11.4 x 10(-7) cm s(-1), n = 12, P < 0.01) and by 67% in porcine coronary venules (from 12.5 x 10(-7) cm s(-1), n = 5, P < 0.05). The response was attenuated in rat mesenteric venules; 10(-4) M N(G)-nitro-l-arginine methyl ester (l-NAME) reduced P(alb)(s) by 23% (from 7.6 x 10(-7) cm s(-1), n = 9, P = 0.01). The inactive d-enantiomers of the NOS inhibitors were without effect on P(alb)(s) in each model. In pig venules, perfusion with blood modified the permeability responses to l-NMMA, suggesting that effects of NO on permeability are modified by one or more elements of blood. These data support a role of nitric oxide release on venular permeability to albumin that is conserved among the three animal species.
authors.affiliation: Department of Medicine and Department of Pediatrics, Baylor College of Medicine, Houston V. A. Medical Center, 2002 Holcombe Blvd., Building 109, Room 114, Houston, Texas 77030, USA. rrumbauot@bcm.tmc.edu
authors.forename: Rolando E
authors.initials: RE
authors.lastname: Rumbaut
authors.forename: Virginia H
authors.initials: VH
authors.lastname: Huxley
mesh_terms: D000418:Albumins / Q000494:pharmacology; D000818:Animals; D002199:Capillary Permeability; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011894:Rana pipiens; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013152:Splanchnic Circulation / Q000187:drug effects; D013552:Swine; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D000418:Albumins; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester