Contractile effects of arginine analogues on human internal thoracic and radial arteries

Objectives: Plasma levels of endogenous guanidino-substituted analogues of L-arginine are increased in various pathologic conditions. In the present s tudy we determined the effects of some of these compounds on basal and stim ulated release of nitric oxide in human internal thoracic and radial arteri es. Methods: Rings of human internal thoracic and radial arteries were obtained from 16 multiorgan donors. The rings were suspended in organ baths for iso metric recording of tension. Results: N-G-monomethyl L-arginine (10(-6) to 10(-3) mol/L) and N-G,N-G- di methyl L-arginine (10(-6) to 10(-3) mol/L) caused concentration- and endoth elium-dependent contractions. Maximal force of contractions for N-G-monomet hyl L-arginine and N-G,N-G-dimethyl L-arginine in the internal thoracic art ery were 18.0% +/- 4.3% and 17.8% +/- 3.8%, respectively, of the contractio n to 100 mmol/L KCl, and those found in the radial artery were 9.6% +/- 2.5 % and 9.1% +/- 2.4%, respectively Aminoguanidine (10(-5) to 3 x 10(-3) mol/ L) and methylguanidine (10(-5) to 3 x 10(-3) mol/L) produced endothelium-in dependent contractions. L-Arginine (10-3 mol/L) prevented the contractions by N-G-monomethyl L-arginine and N-G,N-G-dimethyl L-arginine but did not ch ange contractions induced by aminoguanidine and methylguanidine. N-G-monome thyl L-arginine and N-G,N-G-dimethyl L-arginine inhibited, in a concentrati on-dependent manner, the endothelium-dependent relaxation to acetylcholine in the internal thoracic artery and had little attenuating effect in the ra dial artery; aminoguanidine and methylguanidine were without effect. Conclusions: The results suggest that the contractions induced by N-G-monom ethyl L-arginine and N-G,N-G-dimethyl L-arginine are due to inhibition of b oth basal and stimulated nitric oxide production, whereas aminoguanidine an d methylguanidine do not affect the synthesis of nitric oxide. An increase in the plasma concentration of N-G-monomethyl L-arginine and N-G,N-G-dimeth yl L-arginine is likely to represent a risk factor for abnormal vasomotor t one in conduit arteries used as coronary grafts.