779-2 L-Arginine Does not Acutely Influence Endothelial Function in Either Resistance or Conduit Arteries of Dogs with Pacing Induced Congestive Heart Failure

Abstract

Endothelial function is thought to be abnormal in CHF and this may be due to inadequate endothelial derived relaxing factor (EDRF). L-Arginine, a precursor of EDRF, is therefore postUlated to improve endothelial function in CHF. We studied the effect of L-Arginine (3 mM/min) on endothelial functions in the resistance and conduit arteries (1.8–2.2 mm in size) of dogs before (n = 12) and after (n = 6) inducing heart failure by rapid ventricular pacing, Endothelial function in resistance vessels was assessed by measuring resting and acetylcholine (Ach: 10 -5 to 10 -8 M) stimulated hind limb blood flow (HLBFI and vascular resistance (HLVR) using electromagnetic flow probe before & during intra-arterial L-arginine infusion (3 mM/min). Conduit arteries were studied by measuring isometric tension in a tissue bath system; the effects of serial doses of acetylcholine (10 -5 to 10 -8 M) & sodium nitroprusside (SNP: 10 -5 to 10 -8 M) were evaluated with (1 mM) &without L-arginine in the bath. These effects were repeated in the presence L-NAME (10-5 to 10-8 M). L-Arginine did not influence the HLBF or HLVR at rest or following stimulation with Ach (peak % change in HLVR withfwithout arginine: control 71 ± 7 vs 68 ± 4, P = 0.24 & CHF 82 ± 6 vs 81 ± 3, p = 0.79) or SNP, both in the control or CHF dogs. While Ach had a significantly greater effect in the CHF rings compared to controls (34 vs 14%, p = 0.01), adding L-arginine did not affect developed isometric tension in rings from the conduit arteries before (peak change after Ach withfwithout arginine 16 ± 3% vs 10 ± 4%, p = 0.25) or while in heart failure (33 ± 8 to 36 ± 16%, p = 0.85). Further, L-arginine did not affect the response to L-NAME in either group of dogs (p = 0.65 in controls & p = 0.16 in CHF). These data suggest that L-arginine administration acutely does not influence endothelial function in either conduit or resistance arteries in normal or heart failure dogs.