VASOMOTOR RESPONSE TO PENTOXIFYLLINE MEDIATES IMPROVED RENAL BLOOD-FLOW IN BACTEREMIA

Bacteremia leads to rapid intrarenal vasoconstriction, mediated by end ogenous vasoconstrictors such as TXA2 and endothelin. These changes oc cur before the onset of neutrophil adherence, platelet aggregation, or increases in proinflammatory cytokines. Pentoxifylline (PTX) increase s red cell deformability, reduces neutrophil adhesion, abrogates rises in TNF alpha, and lessens the deleterious effects of other cytokines during prolonged sepsis. PTX also improves renal function in models of established sepsis, but the specific mechanisms of this effect are un clear. Because PTX is a relatively selective visceral vasodilator we s ought to determine whether PTX improves renal microvascular hypoperfus ion during bacteremia and whether the mechanism involves altered vascu lar reactivity. Rat hydronephrotic kidneys were studied by videomicros copy. Interlobular (ILA) arteriolar diameter and flow, afferent (AFP) and efferent (EFF) arteriolar diameters, and cardiac output (GO) were measured at PB-min intervals for 120 min. PTX was infused alone or pri or to a bolus injection of live Escherichia coli. The responses were c ompared to controls infused with equivalent volumes of normal saline a lone. PTX led to improved renal blood flow and to pre- and postglomeru lar vasodilatation. This improvement remained significant compared to bacteremic animals throughout the period of observation. We conclude t hat PTX improves renal blood flow during bacteremia due to pre- and po stglomerular vasodilation. These responses may be a consequence of inc reased intracellular cAMP and release of vasodilator prostanoids. (C) 1996 Academic Press, Inc.