Endothelial Dysfunction and Circadian Blood Pressure Rhythmicity in Young Heart Transplant Recipients

Blood pressure variability correlates with circadian rhythmicity in endothelium-derived nitric oxide (NO) production in adults. Young, hypertensive orthotopic heart transplant (OHT) patients have functional abnormalities in NO-dependent signaling pathways that lead to reduced NO bioavailability and endothelial dysfunction. Following acute intravenous infusion of L-arginine, the amino acid substrate for NO, OHT patients normalize blood pressure (BP) and endothelial function. However, the effects of chronic L-arginine infusion on circadian BP rhythmicity and endothelial function in OHT patients have not been described. Six OHT patients (9–29 years old), and seven healthy control subjects (19–28 years old) were admitted for 48 hours. Systolic, diastolic, and mean blood pressures (MBP) were recorded hourly. Urine samples were obtained to measure nitrates/nitrites (NO_X). Brachial artery flow-mediated vasodilatation (FMD; an index of endothelial function) and left ventricular ejection fraction (LVEF) were measured 0, 23, and 48 hours after admission. Intravenous L-arginine HC1 was infused continuously beginning 24 hours after admission in all subjects. The incidence (50%) and degree (12.0 ± 9.2%) of nocturnal MBP dipping was significantly less in OHT patients than control subjects. Furthermore, FMD was significantly reduced in OHT patients compared to controls (3.2 ± 1.1 vs 7.2 ± 3.1%, p = 0.01). L-Arginine infusion had no significant effect on 24-hour MBP, LVEF, or nocturnal dipping status in any subject; however, L-arginine normalized FMD in OHT patients (7.4 ± 1.8%). Circadian BP variability and endothelial function are impaired in young cardiac transplant patients with medically controlled hypertension, and L-arginine administration reverses endothelial dysfunction.