Ketoprofen significantly attenuated the furosemide-induced increase in plasma renin activity compared to placebo (4.9 vs 10.5 ng/ml/h, p<0.01), suggesting both COX-1 and COX-2 are involved in the renin response.
RCT (n=7)
Latin square design
No
Does COX-1 or COX-2 inhibition alter the saluretic and renin-angiotensin responses to furosemide in healthy cats?
Both COX-1 and COX-2 isoforms appear to mediate the signal from the macula densa to renin-secreting cells in cats exposed to furosemide.
Absolute Event Rate: 4.9% vs 10.5%
p-value: p=<0.01
BACKGROUND: The role of cyclooxygenase(COX)-1 and COX-2 in the saluretic and renin-angiotensin responses to loop diuretics in the cat is unknown. We propose in vivo characterisation of isoform roles in a furosemide model by administering non-steroidal anti-inflammatory drugs (NSAIDs) with differing selectivity profiles: robenacoxib (COX-2 selective) and ketoprofen (COX-1 selective). RESULTS: In this four period crossover study, we compared the effect of four treatments: placebo, robenacoxib once or twice daily and ketoprofen once daily concomitantly with furosemide in seven healthy cats. For each period, urine and blood samples were collected at baseline and within 48 h of treatment starting. Plasma renin activity (PRA), plasma and urinary aldosterone concentrations, glomerular filtration rate (GFR) and 24 h urinary volumes, electrolytes and eicosanoids (PGE2, 6-keto-PGF1α, TxB2), renal injury biomarker excretions N-acetyl-beta-D-glucosaminidase (NAG) and Gamma-Glutamyltransferase were measured. Urine volume (24 h) and urinary sodium, chloride and calcium excretions increased from baseline with all treatments. Plasma creatinine increased with all treatments except placebo, whereas GFR was significantly decreased from baseline only with ketoprofen. PRA increased significantly with placebo and once daily robenacoxib and the increase was significantly higher with placebo compared to ketoprofen (10.5 ± 4.4 vs 4.9 ± 5.0 ng ml(-1) h(-1)). Urinary aldosterone excretion increased with all treatments but this increase was inhibited by 75 % with ketoprofen and 65 % with once daily robenacoxib compared to placebo. Urinary PGE2 excretion decreased with all treatments and excretion was significantly lower with ketoprofen compared to placebo. Urinary TxB2 excretion was significantly increased from baseline only with placebo. NAG increased from baseline with all treatments. Immunohistochemistry on post-mortem renal specimens, obtained from a different group of cats that died naturally of non-renal causes, suggested constitutive COX-1 and COX-2 co-localization in many renal structures including the macula densa (MD). CONCLUSIONS: These data suggest that both COX-1 and COX-2 could generate the signal from the MD to the renin secreting cells in cats exposed to furosemide. Co-localization of COX isoenzymes in MD cells supports the functional data reported here.
Pelligand et al. (Tue,) conducted a rct in Healthy (furosemide-induced renal responses) (n=7). Robenacoxib and Ketoprofen vs. Placebo was evaluated on Increase in plasma renin activity (PRA) from baseline (p=<0.01). Ketoprofen significantly attenuated the furosemide-induced increase in plasma renin activity compared to placebo (4.9 vs 10.5 ng/ml/h, p<0.01), suggesting both COX-1 and COX-2 are involved in the renin response.