Cyclooxygenase 2 and neuronal nitric oxide synthase expression in the renal cortex are not interdependent in states of salt deficiency.
Neuronal nitric oxide synthase (nNOS) and cyclooxygenase-2 (COX-2) expression in the kidney are localized to the cortical thick ascending limb of the loop of Henle (cTALH), including the macula region, and increase after salt restriction. Because of the similar localization and regulation of nNOS and COX-2 expression, we have examined whether there is a functional interrelationship between the expression of the two enzymes. Male Sprague Dawley rats were fed for 1 week either a low-salt diet (0.02% w/w) which produced moderate increases of nNOS and COX-2 expression, or low salt combined with the angiotensin I converting enzyme inhibitor ramipril (10 mg/kg per day), which produced strong increases of renocortical nNOS and COX-2 expressions. To inhibit nNOS or COX-2 activities, animals received in addition N(G)-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg per day) or rofecoxib (10 mg/kg per day) for 1 week, respectively. L-NAME treatment did not change COX-2 expression and conversely rofecoxib treatment did not change nNOS expression in the kidney cortex under any experimental conditions. L-NAME but not rofecoxib attenuated renin mRNA levels. Rofecoxib markedly reduced renal prostanoid excretion. These findings suggest that under these conditions the control of nNOS and COX-2 gene expression in the macula densa regions of the kidney cortex are not dependent on each other.
Castrop
H
H
Institut für Physiologie I, Universität Regensburg, Germany.
Kammerl
M
M
Mann
B
B
Jensen
B L
BL
Krämer
B K
BK
Kurtz
A
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D051546:Cyclooxygenase 2; D004039:Diet, Sodium-Restricted; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D007672:Kidney Cortex / Q000201:enzymology*; D007783:Lactones / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones
D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D017257:Ramipril; D019331:NG-Nitroarginine Methyl Ester