Role of renal nerves in stimulation of renin, COX-2, and nNOS in rat renal cortex during salt deficiency.
We investigated a possible involvement of the sympathetic nervous system in the parallel increase of renin, cyclooxygenase-2 (COX-2), and neuronal nitric oxide synthase (nNOS) gene expression in the juxtaglomerular apparatus of rat kidneys induced by salt deficiency. Therefore, we determined the effects of renal denervation and the beta-adrenoreceptor antagonist metoprolol (50 mg/kg body wt po, twice a day) on renocortical expression of renin, COX-2, and nNOS in rats fed a low-salt (0.02% wt/wt) diet or treated for 1 wk with ramipril (10 mg/kg body wt) in combination with a low-salt diet. We found that a low-salt diet in combination with ramipril strongly increased renocortical mRNA levels of renin, COX-2, and nNOS 9-, 7-, and 2.5-fold, respectively. Treatment with metoprolol did not change basal expression of the three genes or induction of renin and COX-2 gene expression, while induction of nNOS expression was clearly attenuated. Similarly, unilateral renal denervation attenuated induction of nNOS expression but had no effect on all other parameters. These findings suggest that beta-adrenergic stimulation is not required for stimulation of renin and COX-2 gene expression in the juxtaglomerular apparatus during salt deficiency. However, beta-adrenoreceptor activity or renal nerve activity appears to be required for the full stimulation of nNOS expression by low salt intake or combined with angiotensin-converting enzyme inhibition.
Höcherl
K
K
Department of Pharmacology, University of Regensburg, 93040 Regensburg, Germany. klaus.hoecherl@chemie.uni-regensburg.de
Kammerl
M
M
Kees
F
F
Krämer
B K
BK
Grobecker
H F
HF
Kurtz
A
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology; D001794:Blood Pressure; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004039:Diet, Sodium-Restricted; D004298:Dopamine / Q000032:analysis; D004837:Epinephrine / Q000032:analysis; D015971:Gene Expression Regulation, Enzymologic; D006339:Heart Rate; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics*; D007672:Kidney Cortex / Q000737:chemistry / Q000201:enzymology / Q000294:innervation*; D008297:Male; D008565:Membrane Proteins; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000235:genetics*; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D009638:Norepinephrine / Q000032:analysis; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D012083:Renin; D017257:Ramipril; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine