title: Effects of platelet-activating factor on arteriolar and venular tone in rat trachea.
abstract: Platelet-activating factor (PAF) causes altered vascular tone in the mesenteric, pulmonary, and skeletal muscle vascular beds, enhanced macromolecular leak in postcapillary venules, and bronchoconstriction. In spontaneously breathing, anesthetized male Sprague-Dawley rats, we examined responses of individual tracheal microvessels using intravital video microscopy with epi-illumination using a polarizing filter and a long working distance lens (10x). Topical application of PAF (0.1 ml; 10(-9), 10(-7), or 10(-5) M) caused venules (diameter, 51 +/- 5 microm, mean +/- SEM) to constrict in a concentration-dependent fashion. Venoconstriction began within 0-3 min and was maximal within 10 min. In contrast, PAF (10(-5) M) applied to arterioles (diameters, 37 +/- 1 microm) ultimately caused constriction by 21 +/- 7%, but in three dilation (38 +/- 9%) occurred first. PAF (10(-7) and 10(-9) M) applied to arterioles (diameter 36 +/- 3 and 38 +/- 3 microm, respectively) caused no significant change in diameter. Infusion of BN52021, a PAF receptor antagonist, completely blocked constriction of venules and arterioles to PAF (10(-5) M), but dilation (17 +/- 0.2%) still occurred in three of five arterioles. Infusion of Nomega-nitro-l-arginine methyl ester (L-NAME; 1 mg/kg/min), a nitric oxide (NO) synthase inhibitor, potentiated venoconstriction by 34 +/- 18% in response to PAF (10(-7) M) and blocked arteriolar dilation to PAF (10(-5) M). Arteriolar constriction was unaffected by inhibiting NO release. Topical application of L-NAME (10(-3) M) constricted venules (n = 6) by 13 +/- 2% and arterioles (n = 5) by 26 +/- 4%. Venules constricted 33 +/- 15% less to PAF (10(-7) M, n = 5) following topical L-NAME (33 +/- 15%) than with infused l-NAME. Arterioles (n = 5) constricted 27 +/- 4% to PAF (10(-5) M) after topical l-NAME, no different from the group receiving infused L-NAME. We conclude that (1) PAF has a greater vasoconstrictive effect on tracheal venules than arterioles; (2) arterioles have a biphasic response to PAF at some concentrations; (3) PAF-induced vasoconstriction, but not dilation, is receptor mediated; (4) nitric oxide attenuates tracheal venoconstriction and may cause arteriolar dilation in response to PAF; and (5) endogenous release of NO appears to modulate the basal tone of tracheal arterioles more than venules.
authors.affiliation: Critical Care, University of Louisville School of Medicine, Louisville, Kentucky, 40292, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Collins
authors.forename: A M
authors.initials: AM
authors.lastname: Roberts
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D004224:Diterpenes; D004791:Enzyme Inhibitors / Q000494:pharmacology; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000098:blood supply*; D014699:Venules / Q000187:drug effects / Q000378:metabolism
chemical_list: D004224:Diterpenes; D004791:Enzyme Inhibitors; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D009569:Nitric Oxide; C045856:ginkgolide B; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester