915-80 Investigation of Nitric Oxide Release from Human Coronary Arteries with Substance P

Substance P (SP) may be a more useful endothelium-dependent vasodilator in studying coronary vascular function in atherosclerosis, because unlike acetylcholine (ACH). SP has no direct smooth muscle constricting effects. Because dilation has been reported with SP in pts with constriction with ACH, we investigated whether SP causes dilation by releasing nitric oxide (NO) from the human coronary vasculature. The effect of L-NMMA (L-N G monomethyl arginine), a specific inhibitor of NO synthesis, was studied on the coronary vascular effects of SP. The specificity of L-NMMA was tested using the endothelium-independent dilator, sodium nitroprusside (SNP). Fifteen pts with angiographically normal epicardial coronary arteries ( l 20% stenosis) had intracoronary SP (5,10,20 pmol/min) and SNP (40  μ g/min) given before and after L-NMMA (64 μmol/min). Coronary blood flow was measured by Doppler flow wire and diameter by quantitative angiography. Results At baseline, a peak 17 ± 18% (mean ± SO, P l 0.01) increase in distal coronary artery diameter, and a 20 ± 18% (p l 0.01) decrease in coronary vascular resistance (CVR) indicated epicardial and microvascular dilation with SP. At rest, L-NMMA caused a 22 ± 27% increase in CVR and a 13 ± 13% reduction in CA diameter, indicating tonic basal release of NO from coronary epicardial and microvessels. L-NMMA also suppressed the dilatory effects of SP (p l 0.01): after L-NMMA, SP produced an insignificant change in diameter (+1 ± 15%) and CVR was 42% higher compared to control. SNP produced a 19 ± 17% increase in epicardial CA diameter and a 55 ± 20% reduction in CVR at baseline that was not significantly altered by L-NMMA, suggesting that the effects of L-NMMA on the responses to SP are specifically due to inhibition of NO production. Conclusion Human coronary epicardial and microvascular dilation with SP is due, at least partly, to release of NO. Disease-induced differences in responses to endothelium-dependent dilators may be explained by a variation in the extent to which specific receptors on the endothelial surface are affected by pathologic conditions.