INTEGRATING MULTIPLE PARACRINE REGULATORS OF RENAL MICROVASCULAR DYNAMICS

There has been tremendous growth in our knowledge about the multiple i nteracting mechanisms that regulate renal microvascular function. Para crine signals originating from endothelial and epithelial cells exert profound influences on the basal tone and reactivity of the pre- and p ostglomerular arterioles. Selective responsiveness of these arterioles to various stimuli is possible because of differential activating mec hanisms in vascular smooth muscle cells of afferent and efferent arter ioles. Afferent arterioles rely predominantly on voltage-dependent cal cium channels, while efferent arterioles utilize other mechanisms for calcium entry as well as intracellular calcium mobilization. The autor egulatory responses of preglomerular arterioles exemplify the selectiv ity of these complex control mechanisms. The myogenic mechanism respon ds to increases in renal perfusion pressure through ''stretch-activate d'' cation channels that lead to depolarization, calcium entry, and va scular contraction. Autoregulatory efficiency is enhanced by the tubul oglomerular feedback (TGF) mechanism which responds to flow-dependent changes in tubular fluid composition at the level of the macula densa and transmits signals to the afferent arterioles to alter the activati on state of voltage-dependent calcium channels. Recent studies have im plicated extracellular ATP as one paracrine factor mediating TGF and a utoregulatory related signals to the afferent arterioles. Other paracr ine agents including nitric oxide, angiotensin II, adenosine, and arac hidonic acid metabolites modulate vascular responsiveness in order to maintain an optimal balance between the metabolically determined reabs orptive capabilities of the tubules and the hemodynamically dependent filtered load.