Romero-Benavides, Juan Carlos

The effect of prostaglandins (PGs) on proximal sodium reabsorption has not been fully defined. The objective of the present study was to determine the response of proximal tubular sodium reabsorption to infusions of arachidonic acid and specific PGs into the renal interstitium in rats. Renal interstitial infusions of arachidonic acid as well as the individual PGs, I2, E2, and F2 alpha, were employed to elevate the concentration of these PGs in the kidney. Infusion of 10(-4) M arachidonic acid elicited a marked increase of urinary excretion of 6-keto-PGF1 alpha (a stable metabolite of PGI2) from 260.1 +/- 52.7 to 507.4 +/- 129.5 pg/min (P less than 0.05) and a smaller increase of PGE2 from 18.4 +/- 11.2 to 25.9 +/- 10.9 pg/min (P less than 0.05). When micropuncture samples were obtained from superficial late proximal tubules, infusion of arachidonic acid increased the fractional delivery of sodium (FDNa) from 47.8 +/- 5.9 to 58.3 +/- 4.6% (n = 6, P less than 0.01). In the presence of indomethacin, arachidonic acid failed to augment FDNa. Infusion of 10(-5) M PGI2 also increased FDNa from 51.4 +/- 3.4 to 64.0 +/- 4.4% (n = 10, P less than 0.01). PGF2 alpha did not change FDNa and PGE2 decreased it from 53.1 +/- 5.4 to 37.4 +/- 3.3% (n = 8, P less than 0.01). In summary, the present study demonstrates that renal interstitial infusion of arachidonic acid decreases sodium reabsorption by the superficial proximal tubules possibly through the stimulation of PGI2 production.

Hypercholesterolemia (HC) is characterized by increased circulating 8- epi-prostaglandin-F2α(isoprostane), a vasoconstrictor, marker, and mediator of increased oxidative stress, whose vascular effects might be augmented in HC. Anesthetized pigs were studied in vivo with electron beam computed tomography after a 12-wk normal ( n = 8) or HC ( n = 8) diet. Mean arterial pressure (MAP), single-kidney perfusion, and glomerular filtration rate (GFR) were quantified before and during unilateral intrarenal infusions of U46619 (10 ng · kg−1· min−1) or isoprostane (1 μg · kg−1· min−1). Basal renal perfusion and function were similar, and isoprostane infusion elevated its systemic levels similarly in normal and HC (333 ± 89 vs. 366 ± 48 pg/ml, respectively, P < 0.01 vs. baseline). Both drugs markedly and comparably decreased cortical perfusion and GFR in both groups, whereas medullary perfusion decreased significantly only in HC. Moreover, MAP increased significantly only in HC (+9 ± 3 and +11 ± 3 mmHg, respectively, P≤ 0.05). Hence, in HC, renal functional responses to high-dose isoprostane are largely similar to normal, but the systemic circulation exhibits augmented sensitivity to pathophysiological levels of isoprostane and U46619 , which may potentially play a role in development of hypertension and vascular injury associated with increased oxidative stress.