Effects of NG-monomethyl-L-arginine and L-arginine on acetylcholine renal response.

Abstract

Intrarenal infusion of acetylcholine in meclofenamate-treated dogs significantly increased renal blood flow, diuresis, and natriuresis. Intrarenal infusions of either A^'-monomethyl-L-arginine (inhibitor of endothelium-derived relaxing factor formation), or L-arginine (precursor of endothelium-derived relaxing factor formation) did not modify basal levels of those parameters. However, the infusion of A^-monomethyl-L-arginine inhibited the acetylcholineinduced increases in renal blood flow and diuresis without affecting natriuresis, which increased significantly. The infusion of L-arginine failed to further enhance hemodynamic and excretory effects elicited by acetylcholine. I t is well known that the in vitro vascular relaxation induced by acetylcholine (Ach) results from the release of a diffusible relaxing substance, termed endothelium-derived relaxing factor. 1Experimental evidence obtained in these in vitro preparations demonstrates that the endotheliumderived relaxing factor is the free radical nitric oxide.2 -3 Nitric oxide is synthesized from the amino acid L-arginine (L-Arg), 4 and this synthesis is competitively inhibited by A^-monomethyl-L-arginine (LNMMA). 5 The role of nitric oxide in blood pressure regulation has been studied using L N M M A and L-Arg in guinea pigs and rabbits. 6 -7 However, the importance of these actions in vivo is incompletely understood. Ach has been shown to induce the release of endothelium-derived relaxing factor in vitro 1 -2 and when infused intrarenally produces vasodilation accompanied by diuresis and natriuresis. The objective of the present study was to determine whether the vasodilatory and excretory effects of Ach in the dog kidney are mediated by nitric oxide during prostaglandin synthesis inhibition. To address this purpose, we evaluated 1) if the renal vasodilatory and excretory effects of Ach were inhibited in the presence of L N M M A and 2) if these inhibitory effects of L N M M A were abolished by the simultaneous administration of L-Arg. MethodsThe experiment was performed in 16 mongrel dogs of either sex (15-20 kg) anesthetized with sodium pentobarbital (25 mg/kg i.v.). Previously, the dogs had been maintained on a normal diet (sodium 0.42%, potassium 0.71%, calcium 1.6%) and tap water ad libitum. The dogs were ventilated mechanically with a respirator. A femoral artery was cannulated and mean arterial pressure was monitored with a pressure transducer (Statham P23ID, Gould Inc., Hato Rey, Puerto Rico) and recorded on a polygraph (Gould Inc., Cleveland, Ohio). A femoral vein was cannulated for the administration of 2% inulin solution (1 ml/min) and additional anesthetic. The left kidney was exposed through a flank incision, and care was taken not to damage the renal nerves. Renal blood flow (RBF) was measured with a noncannulating electromagnetic flow probe (Carolina Medical Electronics Inc., King, North Carolina) placed around the renal artery. Distal to the flow probe a curved

Endothelium-derived relaxing factor inhibits transport and increases cGMP content in cultured mouse cortical collecting duct cells.

“…3). PD ing 10 Addition of methylene blue (I0-M) alone to M-1 cultures had no significant effect on ISC (51±2 to 54±1 ,uA/cm2) or PD (-37±2 to -39±2 mV). Addition of Bk (10-9 M) to methylene blue-treated M-1 cells in the presence of CPAE cells also produced no significant effect on IS, (54±0.5 to 56±0.5 AA/ cm2) or PD (-40±1 to -39±1 mV).…”

Adaptation to increased dietary salt intake in the rat. Role of endogenous nitric oxide.

“…Acetylcholine infusion has also been reported to have a diuretic and natriuretic effect (33,34). Lahera et al (35) reported that this acetylcholine-induced diuretic effect was dependent on intact NO synthase activity. Thus, in vivo experimental evidence suggests that stimulation of NO synthesis results not only in vasodilatation, but diuresis and natriuresis as well.…”

Role of nitric oxide in renal medullary oxygenation. Studies in isolated and intact rat kidneys.

“…Recent studies have demonstrated an important role for nitric oxide as an endothelial-derived relaxing factor in the regulation ofboth systemic and regional vascular resistances (2,3,15,17). This work was designed to assess the role ofnitrovasodilatation in the homeostasis of intrarenal oxygen supply to the renal medulla, a region normally operating on the verge of hypoxia (6) and therefore likely to have strong vasodilatory mechanisms.…”