CHARACTERIZATION OF A FUNCTIONAL ANGIOTENSIN-IV RECEPTOR ON CORONARY MICROVASCULAR ENDOTHELIAL-CELLS

A new class of angiotensin receptors has recently been identified that exhibits both high specificity and affinity for the hexapeptide (3-8) fragment of angiotensin II, angiotensin IV (AngIV). Here, utilizing r adioligand binding, we fully characterize AngIV binding at the AT4 rec eptor on cultured bovine coronary venular endothelial cells (CVEC), an d report that when AngIV and bFGF are presented simultaneously an enha ncement of DNA synthesis results that is significantly greater than th at produced by bFGF alone. The level of DNA synthesis was determined b y the incorporation of [H-3]thymidine into quiescent CVEC monolayers f ollowing exposure to 10 nM AngIV and 10 ng/ml bFGF for 1, 3, 5, 7, 9, or 11 days. A significant enhancement of DNA synthesis (P < 0.01) was seen following 3, 5, 7, 9 and 11 days exposure. In addition, AngIV doe s not bind to bFGF or heparin, and conversely, bFGF is unable to compe te for AngIV binding which suggests that this synergistic response is mediated by independent receptors for these ligands. Results of this s tudy indicate that microvascular endothelial cells are significantly m ore responsive to bFGF in the presence of nanomolar concentrations of AngIV.