Effects of L- and D-arginine on the basal tone of human diseased coronary arteries and their responses to substance P

Objective-To assess the effects of substance P administration alone and in combination with L- and D-arginine in patients with normal angiograms and i n patients with coronary artery disease. Design-Intracoronary infusions of (a) normal saline, (b) the receptor media ted nitric oxide stimulant substance P (5.6 and 27.8 pmol/min) before and a fter L- or D-arginine (50 and 150 pmol/min), and (c) glyceryl trinitrate (2 50 mu g bolus) were given to 17 patients with coronary artery disease and s table angina, and to six patients with normal angiograms. The diameter of a ngiographically normal proximal and distal segments and coronary stenoses w ere measured by computerised quantitative angiography. Results-L-arginine administration was associated with significant dilatatio n of stenoses (p < 0.01) of proximal segments of both "normal" (p < 0.05) a nd diseased (p < 0.01) arteries, and of distal segments of diseased arterie s (p < 0.01). No significant changes were associated with D-arginine admini stration. Dose dependent dilatation of all segments including stenoses, was observed with substance P both before and after L-arginine infusion (p < 0 .01). The magnitude of dilatation of stenoses and all segments of both "nor mal" and diseased coronaries was greater after L-arginine (p < 0.05) but no t D-arginine and substance P infusion, than it was after saline and substan ce P infusion. Administration of D- or L-arginine did not change the magnit ude of substance P induced dilatation. Conclusions-Diseased and "normal" coronary arteries dilated in response to substance P and L-arginine but were unaffected by D-arginine infusion. The magnitude of the response to substance P was not increased by L-arginine ad ministration, indicating that it is not critically dependent on the availab ility of substrate for nitric oxide synthase.