PERFUSION-INDEPENDENT EFFECT OF BRADYKININ AND FOSINOPRILATE ON GLUCOSE-TRANSPORT IN LANGENDORFF RAT HEARTS

Angiotensin-converting enzyme (ACE) inhibitor-stimulated glucose metab olism and perfusion in muscle tissue seem to be, at least in part, med iated by kinins. However, the relative contribution of direct metaboli c or secondary hemodynamically induced effects is unclear, It was the aim of this study to characterize the effects of ACE inhibition and br adykinin on glucose transport while changes in cardiocoronary function that might influence glucose transport were minimized. Hearts from Wi star rats were perfused by a Langendorff preparation and a set of func tional parameters were simultaneously measured, Bradykinin (10(-11) M) and fosinoprilate (10(-7) M) were administered at concentrations that did not affect coronary flow, Insulin was employed as reference at ha lf-maximal concentration, The nonmetabolizable glucose analog 3-O-[C-1 4]methyl-D-glucose and the nontransportable tracer L-[H-3]glucose were coperfused for the calculation of glucose transport. Using a 2-compar tment mathematical model we found that the glucose transport rate, whi ch was doubled with insulin, was increased almost 3-fold by either bra dykinin or fosinoprilate. In the presence of the B-2 bradykinin recept or antagonist HOE 140 (D-Arg[Hyp(3),Thi(5), D-Tic(7),Oic(8)]-bradykini n; icatibant), the effect of both agents was completely abolished, Bot h agents also induced minor changes in contractility/relaxation parame ters that again were completely neutralized with icatibant, A perfusio n-independent but B-2-kinin receptor-dependent stimulating effect on g lucose transport by either bradykinin or fosinoprilate is concluded, T his effect could, in analogy to insulin be due to increased glucose tr ansporter translocation, increased endothelium-derived nitric oxide fo rmation, or-despite constant coronary flow conditions-secondary to alt ered cardiac function. (C) 1997 by Excerpta Medico, Inc.