Angiotensin II and prostaglandin interactions on systemic and renal effects of L-NAME in humans.
For investigation of whether interactions between prostaglandins and angiotensin II modulate renal response to acute nitric oxide synthesis inhibition in humans, seven young volunteers who were kept on a 240-mM Na diet underwent four experiments with 90 min of infusion of 3.0 microg/kg.min(-1) NG-nitro-L-arginine methyl ester (L-NAME), each preceded by a 3-d treatment with placebo (PL), 50 mg of losartan (LOS), 75 to 125 mg of indomethacin (IND), or both drugs. Mean arterial pressure (MAP), GFR, effective renal plasma flow (ERPF), and Na excretion rate (UNaV) were measured at baseline and from 0 to 45 min and 45 to 90 min of L-NAME infusion. After PL, L-NAME reduced GFR by 5% at 45 min (P < 0.05) and by 9% at 90 min (P < 0.001), ERPF by 11 to 17% (P < 0.001), and UNaV by 28 to 45% (P < 0.001). MAP, unchanged at 45 min, rose by 5% (P < 0.001) at 90 min. LOS prevented pressor but not renal effects of L-NAME. With L-NAME+IND, MAP rose even at 45 min (+5%; P < 0.001 versus baseline) with a 10% rise at 90 min (P < 0.001). Changes in GFR (-13 to -20%), ERPF (-19 to -26%), and UNaV (-51 to -70%) were greater than those with L-NAME+PL or L-NAME+LOS (P < 0.05 to 0.001). With L-NAME+IND+LOS, MAP did not increase, and GFR, ERPF, and UNaV fell much less than with L-NAME+IND alone (P < 0.02 to 0.001) with no differences versus PL or LOS alone. Angiotensin II blockade does not affect renal changes caused by L-NAME but prevents their potentiation by prostaglandin inhibition. Thus, endogenous prostaglandins counteract renal actions of endogenous angiotensin II in Na-repleted humans even when nitric oxide synthesis is inhibited.
Perinotto
Patrizia
P
Istituto di Patologia Medica, Parma, Italy.
Biggi
Almerina
A
Istituto di Semeiotica Medica, University of Parma, Parma, Italy.
Carra
Nicoletta
N
Istituto di Semeiotica Medica, University of Parma, Parma, Italy.
Orrico
Antonella
A
Istituto di Patologia Medica, Parma, Italy.
Valmadre
Giuseppe
G
Istituto di Patologia Medica, Parma, Italy.
Dall'aglio
Pierpaolo
P
Istituto di Patologia Medica, Parma, Italy.
Novarini
Almerico
A
Istituto di Semeiotica Medica, University of Parma, Parma, Italy.
Montanari
Alberto
A
Istituto di Patologia Medica, Parma, Italy.
D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011453:Prostaglandins / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D014661:Vasoconstriction
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D000804:Angiotensin II; D012964:Sodium; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin