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 (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.
Höcherl
Klaus
K
Institut für Pharmakologie, der Universität Regensburg, D-93040 Regensburg, Germany. klaus.hoecherl@chemie.uni-regensburg.de
Kammerl
Martin C
MC
Schumacher
Karl
K
Endemann
Dirk
D
Grobecker
Horst F
HF
Kurtz
Armin
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020910:Ketorolac / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology*; D007783:Lactones / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D013450:Sulfones
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D011453:Prostaglandins; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D013450:Sulfones; C116926:rofecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D012083:Renin; D020910:Ketorolac