Zambraski E J, Atkinson D C, Diamond J
Department of Biology, Rutgers University, New Brunswick, New Jersey.
J Pharmacol Exp Ther. 1988 Oct;247(1):96-103.
The effects of aspirin (acetylsalicylate) (ASA) and nonsteroidal antiinflammatory drugs (NSAIDs) on renal prostaglandin (PG) biosynthesis and function have been studied extensively. In contrast, the in vivo effects of a nonacetylated salicylate (SA), such as sodium SA, on renal function have not been well characterized. No studies have examined the effects of SA on renal function in a situation in which the maintenance of normal kidney function is dependent upon intact renal PG synthesis (i.e., sodium restriction-elevated plasma renin activity). To evaluate the effects of SA vs ASA and/or a NSAID, normal and sodium-restricted anesthetized dogs were treated with SA and then meclofenamate (MECLO) or ASA followed by MECLO. In the normal animals, SA significantly decreased renal PGE2 and PGF2 alpha excretion. After SA a significant amount of MECLO-suppressible PGE2 and PGF2 alpha synthesis remained intact. Compared to SA, with ASA there was a greater decrease in PG excretion, with no further decrease in PG excretion with subsequent MECLO treatment. In the sodium-restricted animals (plasma renin activity, 18-24 ng of angiotensin l/ml/hr) ASA decreased PGE2 excretion but SA did not. In these animals SA did not cause renal vasoconstriction. Additional groups of sodium-restricted animals were studied with extremely high doses of ASA and SA (90 mg/kg) to elevate plasma SA to 200 to 250 micrograms/ml. In these animals SA did decrease PGE2 excretion significantly, but only to levels seen typically in normal animals and, after SA, a large amount of PGE2 excretion could be suppressed by MECLO.(ABSTRACT TRUNCATED AT 250 WORDS)
阿司匹林（乙酰水杨酸）（ASA）和非甾体抗炎药（NSAIDs）对肾脏前列腺素（PG）生物合成及功能的影响已得到广泛研究。相比之下，非乙酰化水杨酸盐（SA），如水杨酸钠，对肾功能的体内影响尚未得到充分表征。尚无研究考察在维持正常肾功能依赖完整肾脏PG合成的情况下（即钠限制-血浆肾素活性升高）SA对肾功能的影响。为评估SA与ASA和/或NSAIDs的作用，对正常和钠限制的麻醉犬给予SA，然后给予甲氯芬那酸（MECLO）或ASA后再给予MECLO。在正常动物中，SA显著降低肾脏PGE2和PGF2α排泄。给予SA后，大量可被MECLO抑制的PGE2和PGF2α合成仍保持完整。与SA相比，ASA使PG排泄下降幅度更大，后续给予MECLO后PG排泄无进一步下降。在钠限制动物中（血浆肾素活性为18 - 24 ng血管紧张素I/ml/小时），ASA降低PGE2排泄，但SA未降低。在这些动物中，SA未引起肾血管收缩。另外几组钠限制动物接受极高剂量的ASA和SA（90 mg/kg）以将血浆SA升高至200至250微克/毫升。在这些动物中，SA确实显著降低了PGE2排泄，但仅降至正常动物通常所见水平，且给予SA后，大量PGE2排泄可被MECLO抑制。（摘要截断于250字）
