Myocardial Contractile Effects of image-Arginine in the Human Allograft

Objectives. In the present study, we investigated, in transplant recipients, whether image-arginine (image-arg) potentiates the myocardial contractile effects of receptor-mediated coronary endothelial stimulation. Moreover, because inducible nitric oxide synthase (iNOS) is frequently expressed in transplanted myocardium, we also performed intracoronary infusion of image-arg in the absence of receptor-mediated coronary endothelial stimulation to investigate whether similar left ventricular (LV) contractile effects could be induced by providing more substrate for iNOS. Background. Nitric oxide (NO), released from coronary endothelium after receptor-mediated stimulation by substance P (SP), affects vascular smooth muscle tone and modulates LV contractile performance. image-arg augments receptor-mediated endothelium-dependent coronary vasodilation in transplant recipients by increasing substrate availability for endothelial NO production. Methods. Sixteen transplant recipients were studied at the time of annual coronary angiography. In eight transplant recipients, microtip LV pressures were recorded before and during intracoronary (IC) SP (20 pmol/min) and after the addition of IC image-arg (160 μmol/min) to IC SP. In eight transplant recipients, microtip LV pressures were recorded before and during IC image-arg (160 μmol/min) alone, and in six of these patients, endomyocardial biopsy samples were obtained to detect the expression of iNOS gene by reverse transcription–polymerase chain reaction. Results. Addition of IC image-arg to IC SP induced fall (mean ± SEM) in LV peak systolic pressure (−16 ± 4 mm Hg), which was larger (p < 0.01) than that observed during IC SP (−7 ± 2 mm Hg). During IC image-arg alone, there was no change in LV peak systolic pressure despite the presence of iNOS mRN in five of the six biopsy samples. Conclusions. In transplant recipients, image-arg potentiates the paracrine myocardial contractile effects of receptor-mediated coronary endothelial stimulation, probably by providing more substrate for endothelial NO production. Despite the myocardial expression of iNOS gene, image-arg alone fails to elicit similar contractile effects.