ACCUMULATION OF AN ENDOGENOUS INHIBITOR OF NITRIC-OXIDE SYNTHASE DURING GRADED HEMORRHAGIC-SHOCK

Asymmetric dimethylarginine (ADMA) represents an endogenous inhibitor of nitric oxide (NO) production, THe production of ADMA has been shown to increase during cellular stress, e.g., hypoxia. Furthermore, ADMA has recently been reported to accumulate in plasma during terminal ren al failure as a consequence of diminished urinary excretion. Since tis sue hypoxia and oliguria are both characteristics of severe hemorrhagi c shock, this study was performed in order to establish whether plasma concentrations of ADMA increase during hemorrhagic shock. Six pigs we re subjected to graded hemorrhage (20% and 40% of the calculated blood volume), resulting in significant (P < 0.05) reductions in blood pres sure and cardiac output (from 98 +/- 4 to 36 +/- 5 mm Hg and from 3.0 +/- 0.2 to 1.4 +/- 0.2 L/min, respectively). Plasma ADMA concentration s as determined by high-performance liquid chromatography (HPLC) incre ased from a pre-hemorrhage value of 3.4 +/- 0.3 mu M to 3.9 +/- 0.4 mu M (ns) and 5.2 +/- 0.4 mu M (P < 0.05), respectively. The present stu dy demonstrates that plasma ADMA concentrations increase significantly during hemorrhagic shock. Thus, inhibition of the arginine-nitric oxi de pathway as a result of ADMA accumulation, may represent an addition al physiological mechanism to maintain systemic blood pressure in resp onse to acute hypovolemia. (c) 1995 Wiley-Liss, Inc.