Effects Of L‐Arginine And Furosemide On Blood Pressure And Renal Function In Volume‐Expanded Rats

Abstract

1. The aim of the present study was to investigate the effects of L-arginine (L-Arg) on blood pressure and water and electrolyte excretion in control and extracellular fluid volume-expanded rats (10% bodyweight with 0.9% NaCl) and to determine whether diuretic treatment with furosemide (FUR) can be optimized by the administration of L-Arg in this model. 2. Both groups of animals were anaesthetized, divided into groups and treated with either 7.5 mg/kg FUR, 250 mg/kg L-Arg, 1 mg/kg NG-nitro-L-arginine methyl ester (L-NAME), FUR + L-NAME or FUR + L-Arg. Mean arterial pressure (MAP), diuresis, natriuresis and kaliuresis were determined. 3. Extracellular fluid volume expansion induced no changes in MAP in control and volume-expanded rats (92+/-6 vs 100+/-8 mmHg, respectively). The hypotension induced by FUR in control and volume-expanded rats (69+/-7 and 76+/-5 mmHg, respectively) was significantly (P < 0.01) enhanced by the administration of L-Arg (54+/-3 and 64+/-3 mmHg, respectively). 4. Injection of L-NAME increased MAP and diminished diuresis, natriuresis and kaliuresis in both groups. 5. Furosemide-induced water and electrolyte excretion was blunted by the administration of L-NAME. 6. The combination of L-Arg + FUR increased diuresis induced by FUR alone (control rats: 29.33+/-1.68 vs 12.91+/- 0.41 microL/min per 100 g, respectively; volume-expanded rats: 248.5+/-25.4 vs 112,6+/-8.3 microL/min per 100 g, respectively; P < 0.01). 7. The administration of the combination of L-Arg + FUR promoted a decrease in the sodium/water excretion ratio compared with the administration of FUR alone (control rats: 0.230+/-0.018 vs 0.45+/-0.03, respectively, P < 0.001; volume-expanded rats: 0.091+/-0.010 vs 0.22+/-0.03, respectively, P < 0.01). 8. The potassium/water excretion rate induced by FUR alone and in the presence of L-Arg followed a pattern similar to that seen for natriuresis (control rats: 0.35+/-0.05 vs 0.20+/-0.05 microEq/min per 100 g, respectively; volume-expanded rats: 0.045+/-0.008 vs 0.014+/-0.003 microEq/min per 100 g, respectively; P < 0.01). 9. The decrease in the electrolyte/water excretion ratio observed with FUR + L-Arg in volume-expanded rats was greater than in control animals. 10. The results of the present study show that the administration of FUR with L-Arg contributes to enhanced hypotensive and diuretic effects of FUR, thus diminishing the relative electrolyte excretion in normal conditions and in extracellular fluid volume expansion.

Inhibition of Vascular Endothelial Growth Factor-A Signaling Induces Hypertension: Examining the Effect of Cediranib (Recentin; AZD2171) Treatment on Blood Pressure in Rat and the Use of Concomitant Antihypertensive Therapy

“…Given there are alternative options available for hypertension management, it may be prudent to avoid this class of antihypertensive for chronic administration with a VEGF signaling inhibitor. Use of some loop diuretics such as furosemide, which blocks renal chloride and sodium reabsorption, should also be avoided as their efficacy is impaired by inhibitors of NO (39). Inhibition of VEGF signaling decreases NO activation acutely, as well as the synthesis of NO synthase chronically (40), which would significantly reduce the effectiveness of furosemide.…”

Everything we always wanted to know about furosemide but were afraid to ask

“…Indeed Tucker and Blantz (159) reported a decrease in mean arterial pressure in animals treated with furosemide, but without volume repletion (159); this was accompanied by a decrease in single nephron glomerular filtration rate (SNGFR), surprisingly mediated by a decrease in glomerular permeability coefficient LpA, but not by a decrease in net ultrafiltration pressure. Surprisingly, Costa et al reported similar decreases in MAP after furosemide administration in rats in normovolemic vs. volume-expanded animals (33). To complicate this further, furosemide could elicit a natriuresis in an individual with decompensated heart failure, leading to a more favorable end-diastolic pressure and increased cardiac output (98).…”

Renal and Vascular Nitric Oxide System in Reduced Renal Mass Saline Hypertension

“…In addition, it was reported that the activation of renal NO pathway induced a diuretic and natriuretic response. Alterations in intrarenal NO production may be involved in the pathogenesis of chronic renal failure [26]. …”