Atrial natriuretic peptide-induced changes in renal prostacyclin production in ureteral obstruction
Ureteral obstruction is characterized by a marked reduction in renal hemodynamic function that is mediated in part by increased production of the vasoconstrictor eicosanoid thromboxane. However, animals with bilateral ureteral obstruction (BUO) sustain less renal functional impairment than unilaterally obstructed (UUO) animals. Recent evidence suggests that atrial natriuretic peptide (ANP) may be important in maintaining these differences. We therefore investigated the possibility that ANP-induced changes in renal arachidonic acid metabolism may be linked to and important in maintaining the differences between BUO and UUO animals. We measured renal function, renal eicosanoid production, and plasma ANP levels in BUO and UUO animals after the release of 24 h of ureteral obstruction. Renal function was reduced in both groups of obstructed animals compared with sham-operated controls. Inulin and p-aminohippurate clearance were significantly increased in BUO compared with UUO animals. Renal 6-ketoprostaglandin F(1α) production by BUO kidneys was also significantly increased compared with kidneys from the UUO group or the sham-operated controls. In contrast, thromboxane B2 production by BUO kidneys was significantly reduced compared with UUO kidneys and was not significantly different from controls. Plasma ANP levels of BUO animals were significantly greater than those of UUO or sham-operated animals. When ANP was administered to in situ perfused UUO or BUO kidneys, renal vascular resistance fell significantly, and ANP induced a dramatic increase in 6-ketoprostaglandin F(1α) production without affecting production of thromboxane B2. Indomethacin blunted the reduction in renal vascular resistance to ANP by 35-50%. These data suggest that differences in BUO and UUO renal function may be related to alterations in circulating ANP levels. In addition, ANP acts as a potent renal vasodilator following ureteral obstruction by means of a direct action and secondarily through stimulation of renal prostacyclin production.
Himmelstein, SI; Coffman, TM; Yarger, WE; Klotman, PE
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