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 (FENa), glomerular filtration rate (GFR), mean arterial pressure (MAP), and plasma renin activity (PRA) were measured before and during renal interstitial infusion of PGE2 (10(-5) M) and/or verapamil (10(-3) M) in rats pretreated with indomethacin. The renal interstitial infusion of PGE2 alone significantly decreased FENa (delta-1.0 +/- 0.2%), whereas the addition of verapamil reversed the effect of PGE2 and significantly increased FENa (delta 2.6 +/- 0.3%, n = 9). The renal interstitial infusion of verapamil alone markedly increased FENa (delta 1.7 +/- 0.3%, n = 7), and this natriuresis was accompanied by a significant decrease in PRA (delta-0.6 +/- 0.1 ng/ml/h, p < 0.05). The addition of PGE2 to the interstitial infusion did not further affect FENa or PRA. There was a significant difference between the effect of interstitial PGE2 infusion and interstitial PGE2 infusion and interstitial verapamil infusion on PRa (delta 1.9 +/- 0.8 vs. delta -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.
Peng
Y
Y
Department of Medicine, Mayo Clinic and Foundation, Rochester, Minn. 55905, USA.
Ramsey
C R
CR
Knox
F G
FG
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors*; D007263:Infusions, Parenteral; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D012965:Sodium Chloride; D014700:Verapamil; D015232:Dinoprostone