Effect of Long-Term Angiotensin II Type I Receptor Antagonism on Peripheral and Coronary Vasomotion
Serotonin constricts coronary arteries with endothelial dysfunction, a common abnormality in cardiac transplant recipients. To assess whether endothelial dysfunction is associated with myocardial blood flow (MBF) abnormalities, 24 patients were studied 1 to 12 months after transplantation. Serotonin in increasing doses (1, 10, and 20 micrograms/min for 2.5 min each) was infused into the coronary circulation. Diameters were measured by quantitative angiography. Fourteen patients (group A) had a pronounced artery constriction (diameter reduction > 40%), while in 10 other patients (group B), such a constriction was never reached. No patient had evidence of rejection and all had angiographically normal coronary arteries. MBF was measured at rest and after intravenous dipyridamole with dynamic nitrogen-13 ammonia positron emission tomography (PET). The resting MBF was higher in group A than in group B (94 +/- 12 vs 74 +/- 15 ml/min/100 g of tissue; p < 0.05). During dipyridamole, MBF was not significantly different (191 +/- 53 vs 184 +/- 64 ml/min/100 g; p = NS). Coronary flow reserve (the ratio of perfusion after dipyridamole to perfusion at rest) was significantly lower in group A than in group B (2.08 +/- 0.54 vs 2.66 +/- 0.57; p < 0.05). Thus, coronary hypersensitivity to serotonin in cardiac transplant recipients is associated with elevated resting MBF and reduced coronary flow reserve. Immune mechanisms inducing endothelial injuries and inflammation-related hyperemia may account for these abnormalities.