We studied the renal effects of the cyclooxygenase inhibitor sodium meclofenamate (M) (5 mg/kg, iv) in the pentobarbital-anesthetized dog that had been maintained on an elevated (100 meq/day) or on a reduced (<5 meq/day) sodium intake, and during the administration of angiotensin II in the sodium-replete dog, or the angiotensin receptor blocker [Sar1–Ala8]angiotensin II in the sodium-deprived dog. In the sodium-replete dog, M did not affect mean arterial blood pressure (MABP), renal blood flow (RBF), glomerular filtration rate (GFR), or urine volume (V), but reduced the urinary excretion of sodium (UNa V) by 47%, and of immunoreactive PGE2 (iPGE2) by 90%. However, in the sodium-replete dog during angiotensin II infusion (3 ng · kg-1 · min-1, iv), M reduced RBF by 35%, GFR by 24%, V by 71%, and iPGE2m by 94%. Similarly, in the sodium-deprived dog M reduced RBF by 34%, GFR by 28%, and iPGE2 excretion by 89%. However, M did not affect RBF or GFR in the sodium-deprived dog during infusion of [Sar1-Ala8]angiotensin II (6 μg · kg-1 · min-1, iv), although iPGE2 excretion was reduced by 84%. This study demonstrates that the effects of M on renal hemodynamics in the dog vary with the state of sodium balance and suggests that a prostaglandin(s) contributes to maintenance of renal blood flow during activation of the renin-angiotensin system. meclofenamate; renal prostaglandins; renin-angiotensin system; receptor blocker; renal hemodynamic and excretory function Submitted on October 17, 1979 Accepted on May 9, 1980
Addition of hydrochlorothiazide to angiotensin receptor blocker therapy can achieve a lower sodium balance with no acceleration of intrarenal renin angiotensin system in patients with chronic kidney disease
