Inhibition by calcium antagonists of shape changes induced in vitro by pro-inflammatory mediators in venous endothelial cells.
The changes in shape of endothelial cells (ECs) lining rat inferior venae cavae in response to exposure in vitro to platelet activating factor (PAF, 5 x 10(-7) M), or 5-hydroxytryptamine creatinine sulphate (5HT, 3 x 10(-5) M), or calcium ionophore A23187 (1 x 10(-5) M), or cytochalasin B (CB, 1 x 10(-5) M) were assessed using an immunofluorescence technique and semi-automated image analysis. Most of these shape changes were prevented by lowering intracellular Ca2+ levels in several ways. Thus, pre-treatment with ryanodine (1 x 10(-6) M), verapamil HCl (2 x 10(-5) M), indomethacin (1 x 10(-4) M), isoprenaline sulphate (2 x 10(-6) M) or dibutyryladenosine 3'5' cyclic monophosphate (DbcAMP, 1 x 10(-5) M) significantly reduced the effects of PAF, 5HT and A23187. Pre-treatment of ECs with 8(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate HCl (TMB-8, 1 x 10(-5) M) or the nominal absence of Ca2+ in the extracellular medium prevented the effects of PAF and 5HT, but not those of A23187. The responses to 5HT were also reduced by cyproheptadine HCl (3 x 10(-6) M). However, only the absence of extracellular Ca2+ reduced the effects of CB. The calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide HCl (W7, 1 x 10(-5) M) and the protein kinase C inhibitor 1-(5-isoquinolinyl sulphanyl)-2-methylpiperazine 2HCl (H7, 1 x 10(-5) M) were without effect against all the above agonists, but H7 and verapamil prevented EC shape changes induced by phorbol myristate acetate (PMA, 1 x 10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Northover
A M
AM
Department of Pharmacy, School of Health and Life Sciences, Leicester Polytechnic, UK.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D006651:Histocytochemistry; D066298:In Vitro Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D013194:Staining and Labeling; D014682:Vena Cava, Inferior / Q000166:cytology / Q000187:drug effects
D002121:Calcium Channel Blockers