EDRF released from microvascular endothelial cells dilates arterioles in vivo
Koller, A.; Seyedi, N.; Gerritsen, M.E.; Kaley, G.
American Journal of Physiology 261(1 Pt 2): H128-H133
1991
ISSN/ISBN: 0002-9513 PMID: 1858912 Document Number: 385107
Microvascular endothelial cells (MECs) from rat epididymal fat pad were isolated and cultured in vitro on Cytodex 3 microcarrier beads. In Krebs-suffused cremaster muscle of pentobarbital-anesthetized rats anteriolar diameters (mean control diam 20.9 .+-. 0.9 .mu.m) were measured using image shearing video microscopy. Two lines of suffusate (1.5 mg/min each) were established; one contained a column of microcarrier beads only (no cells in line; NC) the other contained a 1-ml column of MECs grown on beads (through cells; TC). The muscle preparation and the MECs were first treated with indomethacin (Indo; 28 UmM). Indo treatment blocked arteriolar dilation to A23187 (1 .mu.M) and arachidonic acid (AA; 0.25 .mu.M) administered into the NC line. A 4.0 .+-. 0.6 .mu.m increase in arteriolar diameter was observed, however, when A23187 (but not AA) was infused through the TC line containing Indotreated MECs on beads. The A23187-elicited dilation was abolished by the introduction of NG-monomethyl-L-arginine (L-NMMA; 200 .mu.M) into the TC line. Administration of atropine (2 .mu.M) onto the cremaster muscle via the NC line inhibited the dilations in response to acetylcholine (ACh; 2.7 .mu.M) given through the NC line. Infusion of ACh through the TC line onto the atropine-treated cremaster muscle, however, elicited a 5.8 .+-. 1.3 .mu.m increase in arteriolar diameter, a response that was blocked by prior administration of L-NMMA into the TC line. Arteriolar dilation induced by adenosine (0.5 .mu.M) of sodium nitroprusside (0.5 .mu.M) applied via the NC or TC line was unaffected by L-NMMA. Results of our experiments suggest that cultured microvascular endothelial cells are able to release in basal conditions and upon stimulation by agonists, a non-prostaglandin vasodilator principle that has the attributes of endothelium-derived relaxing factor.