Role of prostanoids in regulation of the renin-angiotensin-aldosterone system by salt intake

We investigated the effect of cyclooxygenase (COX) activity on the regulation of the renin-angiotensin-aldosterone system by salt intake. Therefore, Sprague-Dawley rats were subjected to different salt diets [0.02, 0.6, and 8% NaCl (wt/wt)] and treated with the selective COX-2 inhibitor rofecoxib (1...

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Bibliographic Details
Published in:	American journal of physiology. Renal physiology Vol. 283; no. 2; p. F294
Main Authors:	Höcherl, Klaus, Kammerl, Martin C, Schumacher, Karl, Endemann, Dirk, Grobecker, Horst F, Kurtz, Armin
Format:	Journal Article
Language:	English
Published:	United States 01-08-2002
Subjects:	Animals Blood Pressure - drug effects Blood Pressure - physiology Cyclooxygenase 1 Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors - pharmacology Gene Expression Regulation, Enzymologic - drug effects Gene Expression Regulation, Enzymologic - physiology Immunohistochemistry Isoenzymes - antagonists & inhibitors Isoenzymes - genetics Isoenzymes - metabolism Ketorolac - pharmacology Kidney - enzymology Lactones - pharmacology Male Membrane Proteins Prostaglandin-Endoperoxide Synthases - genetics Prostaglandin-Endoperoxide Synthases - metabolism Prostaglandins - metabolism Rats Rats, Sprague-Dawley Renin - genetics Renin-Angiotensin System - drug effects Renin-Angiotensin System - physiology RNA, Messenger - analysis Sodium Chloride, Dietary - pharmacology Sulfones
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Summary:	We investigated the effect of cyclooxygenase (COX) activity on the regulation of the renin-angiotensin-aldosterone system by salt intake. Therefore, Sprague-Dawley rats were subjected to different salt diets [0.02, 0.6, and 8% NaCl (wt/wt)] and treated with the selective COX-2 inhibitor rofecoxib (10 mg x kg body wt(-1) x day(-1)) or with ketorolac at a dose selective for COX-1 inhibition (2 mg x kg body wt(-1) x day(-1)) for 3, 7, 14, and 21 days. Rofecoxib and ketorolac caused a similar reduction of renocortical PGE2 formation with a low-salt diet. Rofecoxib did not change plasma renin activity or renocortical renin mRNA abundance with any of the diets but clearly lowered plasma aldosterone concentration. In contrast, ketorolac delayed the increase in plasma renin activity and of renin mRNA in response to low salt intake but did not change plasma aldosterone concentration. Prolonged treatment with rofecoxib but not with ketorolac caused an upregulation of COX-2 expression while COX-1 mRNA abundance remained unchanged. These findings suggest that COX-1-derived, but not COX-2-derived, prostanoids are of relevance for the regulation of the renin system by salt intake.
ISSN:	1931-857X
DOI:	10.1152/ajprenal.00347.2001