Acquired essential fatty acid depletion in the remnant kidney: amelioration with U-63557A.
Previous studies have demonstrated an association between renal cortical fatty acid composition and experimental models of renal injury. The present study was designed to extend these observations to the remnant kidney and to investigate the hypothesis that increased endogenous turnover of arachidonic acid metabolites results in the depletion of progenitor fatty acids. Remnant kidney cortex demonstrated a relative reduction of the essential fatty acids, linoleate and arachidonate (20 +/- 7.2% and 11 +/- 0.3%, respectively), nine weeks after subtotal nephrectomy. In addition, the monounsaturated fatty acid, oleate, was increased (48 +/- 10.6%) while its saturated progenitor, stearate, was decreased (13 +/- 4.3%). Serial evaluation of dienoic prostanoids revealed a significant increase in the renal excretion of TXB2 in rats with remnant kidneys (27 +/- 3.0, 29 +/- 1.1, and 34 +/- 3.3 ng/day vs. 21 +/- 0.8, 20 +/- 1.5, and 22 +/- 3.3 ng/day in control rats, at 3, 6, and 9 weeks, respectively). Moreover, TXB2 excretion inversely correlated with dienoic progenitor fatty acids [18:2(n-6), r2 = 0.76; 20:4(n-6), r2 = 0.79], suggesting that these events are biochemically coupled. Endogenous turnover of precursor fatty acids, confirmed by an increase in renal TXB2 excretion, preceded overt depletion of essential fatty acids by several weeks. Importantly, blockade of endogenous synthesis of TXA2 with the specific TXA2 synthase antagonist, U-63557A, restored the essential fatty acid composition to normal and ameliorated progressive glomerular destruction. Moreover, the ancillary fatty acid disturbances were attenuated by administration of U-63557A.(ABSTRACT TRUNCATED AT 250 WORDS)
Schmitz
P G
PG
Department of Internal Medicine, Saint Louis University, Missouri.
Krupa
S M
SM
Lane
P H
PH
Reddington
J C
JC
Salinas-Madrigal
L
L
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D015232:Dinoprostone / Q000652:urine; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005228:Fatty Acids, Essential / Q000172:deficiency* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000652:urine; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013997:Time Factors
D001572:Benzofurans; D005227:Fatty Acids; D005228:Fatty Acids, Essential; D013929:Thromboxane B2; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase; D015232:Dinoprostone; C039936:furegrelate