Endothelin-1 May Be a Potential Biomarker for Monitoring Changes in Nitric Oxide Metabolism in Pulmonary Hypertension

Pulmonary hypertension (PH) is characterized by endothelial cell dysfunction and dysregulation of endogenous nitric oxide (NO) synthesis. NO bioavailability is further decreased due to dysregulation of the oral microbiome and reduction of dietary nitrate (NO3-) to nitrite (NO2-). PH biomarkers such as NT-proBNP have been associated with disease severity, prognosis and response to therapy. Emerging biomarkers like Endothelin-1 (ET-1) reflect NO signaling and cellular dysregulation. We evaluated the effect of a single dose of nitrate on NT-proBNP, ET-1, NO3- and NO2- levels in PH patients versus controls. Patients with prior right heart catheterization were administered 1000mg of sodium nitrate orally. Plasma NT-proBNP, ET-1, NO3- and NO2- were measured at baseline, 2, 6, and 24 hours following nitrate drug administration. Response of patients with PH (mPAP ≥ 25mmHg, TPG ≥ 12mmHg) was compared to controls (mean PAP Nine patients were evaluated (control: n=4, age 53 ± 14 years, 100% female, EF 55 ± 0%, mPAP 19 ± 4 mmHg, PCWP 11 ± 3 mmHg, TPG 9 ± 4 mmHg, PVR 1.5 ± 0.6 WU; PH: n=5, age of 59 ± 9 years, 80% female, EF 58 ± 8%, mPAP 41 ± 8 mmHg, PCWP 26 ± 7 mmHg, TPG 14 ± 3 mmHg, PVR 2.9 ± 0.7 WU). Following oral nitrate dose, mean plasma NO3- and NO2- levels increased in both groups. NO3- levels were significantly greater in the control vs PH group at 2 hrs (803 ± 404 µm vs 571 ± 202 µm) and 6 hrs (634 ± 254 µm vs 482 ± 183 µm) (overall P