Reversal of the antinatriuretic effect of prostaglandin e₂ by verapamil in the rat

Previous studies have demonstrated that prostaglandin E₂ (PGE₂) infusion increases intrarenal angiotensin-II (ANG-II) formation and decreases sodium excretion in the rat. PGE₂ infusion may have direct tubular effects or indirect effects through increased intrarenal ANG-II. In the present study, the calcium channel blocker verapamil was used to determine whether it would reverse the PGE₂-induced decrease in sodium excretion. To minimize any systemic and hemodynamic influences, verapamil and PGE₂ were infused directly into the renal interstitium via a chronically implanted matrix. Fractional sodium excretion (FE_Na), glomerular filtration rate (GFR), mean arterial pressure (MAP), and plasma renin activity (PRA) were measured before and during renal interstitial infusion of PGE₂ (10^-5M) and/or verapamil (10^-3M) in rats pretreated with indomethacin. The renal interstitial infusion of PGE₂ alone significantly decreased FE_Na (Δ-1.0 ± 0.2%), whereas the addition of verapamil reversed the effect of PGE₂ and significantly increased FE_Na (Δ2.6 ± 0.3%, n = 9). The renal interstitial infusion of verapamil alone markedly increased FE_Na (Δ1.7 ± 0.3%, n = 7), and this natriuresis was accompanied by a significant decrease in PRA (Δ-0.6 ± 0.1 ng/ml/h, p < 0.05). The addition of PGE₂ to the interstitial infusion did not further affect FE_Na or PRA. There was a significant difference between the effect of interstitial PGE₂ infusion and interstitial verapamil infusion on PRA (Δ1.9 ± 0.8 vs. Δ-0.6 ± 0.1 ng/ml/h, p < 0.05). GFR and MAP remained unchanged in response to the renal interstitial infusion of PGE₂ and/or verapamil. In conclusion, verapamil reversed the PGE₂-induced antinatriuresis in the rat.