Key result
Benazepril decreases ACE activity but fails to prevent furosemide-induced RAAS activation.
Why the study?
Does benazepril prevent furosemide-induced RAAS activation in healthy dogs?
Does benazepril prevent furosemide-induced RAAS activation in healthy dogs?
Absolute Event Rate: 0.99% vs 1.1%
p-value: p=<0.05
In healthy dogs, benazepril suppresses ACE activity but fails to prevent furosemide-induced aldosterone breakthrough even at the initiation of therapy.
Benazepril fails to prevent furosemide-induced aldosterone breakthrough in dogs; leaves open whether ACEIs mitigate RAAS activation during diuretic therapy.
Pilot studies in our laboratory revealed that furosemide-induced renin-angiotensin-aldosterone system (RAAS) activation was not attenuated by the subsequent co-administration of benazepril. This study was designed to evaluate the effect of benazepril on angiotensin-converting enzyme (ACE) activity and furosemide-induced circulating RAAS activation. Our hypothesis was that benazepril suppression of ACE activity would not suppress furosemide-induced circulating RAAS activation, indicated by urinary aldosterone concentration. Ten healthy hound dogs were used in this study. The effect of furosemide (2 mg/kg p.o., q12h; Group F; n = 5) and furosemide plus benazepril (1 mg/kg p.o., q24h; Group FB; n = 5) on circulating RAAS was determined by plasma ACE activity, 4-6 h posttreatment, and urinary aldosterone to creatinine ratio (UAldo:C) on days -1, -2, 1, 3, and 7. There was a significant increase in the average UAldo:C (μg/g) after the administration of furosemide (Group F baseline [average of days -1 and -2] UAldo:C = 0.41, SD 0.15; day 1 UAldo:C = 1.1, SD 0.56; day 3 UAldo:C = 0.85, SD 0.50; day 7 UAldo:C = 1.1, SD 0.80, P < 0.05). Benazepril suppressed ACE activity (U/L) in Group FB (Group FB baseline ACE = 16.4, SD 4.2; day 1 ACE = 3.5, SD 1.4; day 3 ACE = 1.6, SD 1.3; day 7 ACE = 1.4, SD 1.4, P < 0.05) but did not significantly reduce aldosterone excretion (Group FB baseline UAldo:C = 0.35, SD 0.16; day 1 UAldo:C = 0.79, SD 0.39; day 3 UAldo:C 0.92, SD 0.48, day 7 UAldo:C = 0.99, SD 0.48, P < 0.05). Benazepril decreased plasma ACE activity but did not prevent furosemide-induced RAAS activation, indicating aldosterone breakthrough (escape). This is particularly noteworthy in that breakthrough is observed at the time of initiation of RAAS suppression, as opposed to developing after months of therapy.
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Lantis et al. (2014) studied Healthy dogs (n=10). Benazepril added to furosemide vs. Furosemide alone was evaluated on Urinary aldosterone to creatinine ratio (UAldo:C) (p=<0.05). Benazepril decreased plasma ACE activity but did not prevent furosemide-induced RAAS activation, with day 7 urinary aldosterone:creatinine reaching 0.99 μg/g versus 1.1 μg/g with furosemide alone.
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