Donor L-arginine Research Articles

Constitutive nitric oxide release is impaired after ischemia and reperfusion

Myocardial ischemia and reperfusion may result in endothelial dysfunction and reduced release of nitric oxide. With the use of an amperometric sensor, the first direct measurements of constitutive nitric oxide release from a beating heart were measured from the coronary effluent of isolated working rat hearts subjected to ischemia and reperfusion. Rats, six to eight per group, were randomly studied as follows: control (no pretreatment) and pretreatment with the nitric oxide donor L-arginine (3 mmol/L), its enantiomer D-arginine (3 mmol/L), nitric oxide inhibitor N omega-nitro-L-arginine methyl ester (100 mumol/L), and combined N omega-nitro-L-arginine methyl ester/L-arginine. Isolated hearts were pretreated for 10 minutes before 30 minutes of global ischemia and 30 minutes of reperfusion. A nonischemic control group (n = 4) was continuously perfused with oxygenated unsupplemented buffer. After ischemia/reperfusion, hearts supplemented with L-arginine recovered significantly (p < 0.05) increased developed pressure, first derivative of the aortic pressure (dP/dtmax), and aortic flow compared with all other hearts that underwent ischemia/reperfusion. In addition, nitric oxide release was significantly (p < 0.05) increased during reperfusion in the L-arginine group. During reperfusion, the recovery of aortic flow correlated with nitric oxide release (r = 0.81, p < 0.0001). We conclude that after ischemia/reperfusion, endothelial dysfunction results in decreased nitric oxide release, which can be ameliorated with L-arginine pretreatment. The direct cytoprotective properties of nitric oxide may contribute to improved functional recovery in hearts pretreated with L-arginine. Augmentation of the L-arginine/nitric oxide pathway may provide a new approach for improved recovery after cardiovascular operations.

Inhibition by L-arginine of the endothelin-mediated increase in cytosolic calcium in human neutrophils

The effect of endothelin (ET) on the cytosolic-free calcium ([Ca 2+] i) changes in polymorphonuclear leukocytes (PMN) from normal humans and Wistar rats was investigated. ET induced a dose-related [Ca 2+] i peak. This [Ca 2+] i transient was blunted by TMB-8 (10 −5M) and by Ca 2+-free EGTA medium, therefore suggesting a role of both intracellular Ca 2+ release and Ca 2+ influx in the generation of the [Ca 2+] i peak. Preincubation of PMN with the nitric oxide (NO)-donor L-arginine (L-Arg) markedly blocked the ET-induced [Ca 2+] i transient in an enantiomerically-specific manner. A similar blunting effect of L-Arg on the fMLP (10 −7M)-induced [Ca 2+] i transient was detected. The L-Arg antagonist, N G-monomethyl-L-arginine (L-NMMA), reverted the L-Arg blocking effect on both ET- and fMLP-induced [Ca 2+] i transients. These data suggest that ET has a potential role in activating Ca 2+ mobilization in PMN, an effect that can be inhibited by L-Arg.