Vasomotor response to pentoxifylline mediates improved renal blood flow to bacteremia.
Bacteremia leads to rapid intrarenal vasoconstriction, mediated by endogenous vasoconstrictors such as TXA2 and endothelin. These changes occur before the onset of neutrophil adherence, platelet aggregation, or increases in proinflammatory cytokines. Pentoxifylline (PTX) increases red cell deformability, reduces neutrophil adhesion, abrogates rises in TNFalpha, 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 unclear. Because PTX is a relatively selective visceral vasodilator we sought to determine whether PTX improves renal microvascular hypoperfusion during bacteremia and whether the mechanism involves altered vascular reactivity. Rat hydronephrotic kidneys were studied by videomicroscopy. Interlobular (ILA) arteriolar diameter and flow, afferent (AFF) and efferent (EFF) arteriolar diameters, and cardiac output (CO) were measured at 15-min intervals for 120 min. PTX was infused alone or prior to a bolus injection of live Escherichia coli. The responses were compared to controls infused with equivalent volumes of normal saline alone. PTX led to improved renal blood flow and to pre- and postglomerular vasodilatation. This improvement remained significant compared to bacteremic animals throughout the period of observation. We conclude that PTX improves renal blood flow during bacteremia due to pre- and postglomerular vasodilation. These responses may be a consequence of increased intracellular cAMP and release of vasodilator prostanoids.
Krysztopik
R J
RJ
Department of Surgery, Veterans Administration Medical Center, Louisville, Kentucky, USA.
Bentley
F R
FR
Wilson
M A
MA
Spain
D A
DA
Garrison
R N
RN
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D016470:Bacteremia / Q000503:physiopathology*; D001794:Blood Pressure; D002302:Cardiac Output / Q000187:drug effects; D004927:Escherichia coli Infections / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006869:Hydronephrosis / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D010431:Pentoxifylline