Eicosanoid regulation of the renal vasculature

Even though it has been recognized that arachidonic acid metabolites, eicosanoids, play an important role in the control of renal blood flow and glomerular filtration, several key observations have been made in the past decade. One major finding was that two distinct cyclooxygenase (COX-1 and COX-2) enzymes exist in the kidney. A renewed interest in the contribution of cyclooxygenase metabolites in tubuloglomerular feedback responses has been sparked by the observation that COX-2 is constitutively expressed in the macula densa area. Arachidonic acid metabolites of the lipoxygenase pathway appear to be significant factors in renal hemodynamic changes that occur during disease states. In particular, 12(S)- hydroxyeicosatetraenoic acid may be important for the full expression of the renal hemodynamic actions in response to angiotensin II. Cytochrome P-450 metabolites have been demonstrated to possess vasoactive properties, act as paracrine modulators, and be a critical component in renal blood flow autoregulatory responses. Last, peroxidation of arachidonic acid metabolites to isoprostanes appears to be involved in renal oxidative stress responses. The recent developments of specific enzymatic inhibitors, stable analogs, and gene-disrupted mice and in antisense technology are enabling investigators to understand the complex interplay by which eicosanoids control renal blood flow.