Beta 2-adrenoceptors mediate a reduction in endothelial permeability in vitro.
The permeability of bovine pulmonary artery endothelial (CPAE) monolayers to Evans blue-labelled albumin (Evans blue-albumin) has been measured in vitro. Thrombin caused a concentration-dependent increase in Evans blue-albumin clearance across endothelial monolayers. Isoprenaline inhibited thrombin-induced Evans blue-albumin clearance in a concentration-dependent manner (EC50 21 nM). This effect was mimicked by the selective beta 2-adrenoceptor agonists salbutamol (EC50 64 nM) and salmeterol (EC50 2.7 nM), but not by the selective beta 1-adrenoceptor agonist, RO-363 ((1-[3',4'-dihydroxyphenoxy]-2-hydroxy-[3",4"- dimethoxyphenethylamino]-propane)oxalate), nor by the selective beta 3-adrenoceptor agonist, CL-316,243 (disodium (R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]-1,3- benzodioxole-2,2-dicarboxylate). Isoprenaline, salbutamol and salmeterol, but not RO-363 or CL-316,243 produced small, but significant reductions in Evans blue-albumin clearance across unstimulated endothelial monolayers. Inhibition of the response to thrombin by isoprenaline was antagonised by the selective beta 2-adrenoceptor antagonist, ICI-118,551 ((erythro-DL-1(7-methylindan-4- yloxy)3-isopropylaminobutan-2-ol), pKB 8.4). Salmeterol also inhibited hydrogen peroxide-stimulated Evans blue-albumin clearance. Hence, the widely used beta 2-adrenoceptor agonists, salbutamol and salmeterol, are able to reduce endothelial permeability at nanomolar concentrations.
Allen
M J
MJ
Department of Pharmacology 1, Glaxo Research & Development Ltd., Ware, Herts, UK.
Coleman
R A
RA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000418:Albumins / Q000737:chemistry; D000420:Albuterol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002396:Catechols; D002417:Cattle; D002478:Cells, Cultured; D004149:Dioxoles / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005070:Evans Blue / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007545:Isoproterenol / Q000378:metabolism / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011412:Propanolamines / Q000378:metabolism / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000068299:Salmeterol Xinafoate; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000418:Albumins; D002396:Catechols; D004149:Dioxoles; D008070:Lipopolysaccharides; D011412:Propanolamines; D011450:Prostaglandin Endoperoxides, Synthetic; D018343:Receptors, Adrenergic, beta-2; D014662:Vasoconstrictor Agents; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D009599:Nitroprusside; D005070:Evans Blue; C026777:ICI 118551; D013928:Thromboxane A2; D000068299:Salmeterol Xinafoate; C018420:Ro 363; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D006861:Hydrogen Peroxide; D013917:Thrombin; D007545:Isoproterenol; D000420:Albuterol