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

Abstract

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.