Role of renal nerves in stimulation of renin, COX-2, and nNOS in rat renal cortex during salt deficiency

Abstract

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.

Cyclooxygenases, the Kidney, and Hypertension

“…20 Most but not all experimental studies have supported a role for COX-2 in MD mediation of renin release. 14,19,[21][22][23][24][25] In isolated perfused glomerular preparations, renin release induced by MD perfusion with a low chloride solution was inhibited by a COX-2 inhibitor but not a COX-1 inhibitor. 22 In vivo studies in rats indicated that increased renin release in response to low-salt diet, ACEI, loop diuretics, or aortic coarctation could be inhibited by administration of COX-2-selective inhibitors.…”

Update on Cyclooxygenase-2 Inhibitors

“…Studies using experimental animals have indicated that selective COX-2 inhibitors can significantly decrease plasma renin levels, renal renin activity, and mRNA expression under certain high-renin states (69 -75). Most (43,64,66,69,70,76 -78) but not all experimental studies (79,80) have indicated a role for COX-2 in MD mediation of renin release. Randomized crossover studies in healthy humans who were administered furosemide and/or a low-sodium diet demonstrated inhibition of renin release by the COX-2 inhibitors rofecoxib (43) and meloxicam (81).…”

Cyclooxygenase-2 Inhibition Attenuates Lipopolysaccharide-Induced Cardiovascular Failure

“…32 Determination of NOS-II, COX-1, COX-2, and ␤-Actin mRNA Total RNA (50 g) from the heart, lung, and liver was extracted, and the abundance of NOS II mRNA, COX-1 mRNA, and COX-2 mRNA was semi-quantitated and related to ␤-actin mRNA (1 g) by specific RNase protection assay as described. 8,33 Determination of Nitrate/Nitrite, PGE 2 , and 6-Keto PGF 1␣ Nitrate/nitrite concentrations and concentrations of PGE 2 and 6-keto prostaglandinF 1␣ in plasma and liver were determined using commercially available assay kits (Cayman Chemical).…”

“…33 Total protein (100 g) from liver and lung was determined by using a mouse monoclonal antibody against NOS II (BD Transduction Laboratories), rabbit polyclonal antibodies against COX-1 or COX-2 (Cayman), and a horseradish peroxidase-conjugated secondary antibody (BD Transduction Laboratories for NOS II and Santa Cruz for COX).…”