MYOCARDIAL CONTRACTILE EFFECTS OF L-ARGININE IN THE HUMAN ALLOGRAFT

Objectives. In the present study, we investigated, in transplant recip ients, whether L-arginine (L-arg) potentiates the myocardial contracti le effects of receptor-mediated coronary endothelial stimulation. More over, because inducible nitric oxide synthase (iNOS) is frequently exp ressed in transplanted myocardium, we also performed intracoronary inf usion of L-arg in the absence of receptor-mediated coronary endothelia l stimulation to investigate whether similar left ventricular (LV) con tractile effects could be induced by providing more substrate for iNOS . Background. Nitric oxide (NO), released from coronary endothelium af ter receptor-mediated stimulation by substance P (SP), affects vascula r smooth muscle tone and modulates LV contractile performance, L-arg a ugments receptor-mediated endothelium-dependent coronary vasodilation in transplant recipients by increasing substrate availability for endo thelial NO production. Methods. Sixteen transplant recipients were stu died at the time of annual coronary angiography. In eight transplant r ecipients, microtip LV pressures were recorded before and during intra coronary (IC) SP (20 pmol/min) and after the addition of IC L-arg (160 mu mol/min) to IC SP. In eight transplant recipients, microtip LV pre ssures were recorded before and during IC L-arg (160 mu mol/min) alone , and in six of these patients, endomyocardial biopsy samples were obt ained to detect the expression of iNOS gene by reverse transcription-p olymerase chain reaction. Results. Addition of IC L-arg to IC SP induc ed a 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 L-arg alone, there was no change in LV peak systo lic pressure despite the presence of iNOS mRNA in five of the six biop sy samples. Conclusions. In transplant recipients, L-arg potentiates t he paracrine myocardial contractile effects of receptor mediated coron ary endothelial stimulation, probably by providing more substrate for endothelial NO production, Despite the myocardial expression of iNOS g ene, L- arg alone fails to elicit similar contractile effects. (C) 199 7 by the American College of Cardiology.