Renal responses to intra‐arterial infusion of a peroxynitrite scavenging agent with or without angiotensin II in anesthetized rats (1134.4)

Abstract

Peroxynitrite (OONO‐) is continually formed in the biological tissue by the spontaneous reaction between nitric oxide and superoxide. However, its potential role in the regulation of renal hemodynamics and excretory function in control condition as well as in the condition of elevated angiotensin II (AngII) level is not yet clearly defined. In the present study, we examined the responses to a OONO‐ scavenging agent, mercaptoethyl guanidine (MEG; 5 µg/kg/min for 75 min) infused directly into the left renal artery in anesthetized (Inactin; 100 mg/kg; i.p.) rats pretreated with (n=5) or without (n=5) AngII (1 ng/kg/min). The MEG dose was effective in blocking the increased renal blood flow (RBF) response to a bolus dose infusion of OONO‐ (40 µg/kg). RBF was recorded by the Transonic flow probe placed on the left renal artery and glomerular filtration rate (GFR) was determined by inulin clearance. In control rats (n=5), MEG infusion did not alter renal vascular resistance (RVR), RBF or GFR but caused significant decreases in urine flow (V, 9.5±1.4 to 7.8±1.5 μL/min/g; ‐20.2±6.7%), sodium excretion (UNaV, 1.69±0.38 to 1.34±0.43 μmol/min/g; ‐29.3±14.2%) and in fractional excretion of sodium (FENa, 1.04±0.33 to 0.87±0.36%; ‐29.3±15%). In a separate group (n=5), AngII treatment caused an increase of 18.0±4.1% in RVR (baseline value, b; 14.8±1.9 mmHg/mL/min/g) and the decreases of 14.4±3.6% in RBF (b, 7.2 mL/min/g), 17.1±6.2% in V (b, 6.7±2.3 μL/min/g), 35.6±14.4% in UNaV (b, 1.17±0.61 μmol/min/g) and 37.4±12.5% in FENa (b, 0.9±0.6%) without appreciable change in GFR. However, MEG infusion in these AngII treated rats caused similar decreases in renal excretory parameters (‐19.7±10.9% in V, ‐31.8±13.4% in UNaV and ‐33.3±8.4% in FENa) without significant changes in RVR, RBF or GFR. These data indicate that the endogenous OONO‐ exerts minimal hemodynamic effect but contributes to the maintenance of renal excretory function both in control condition as well as in the condition of elevated AngII level.