Renal and Hormonal Effects of Systemic Nitric Oxide Inhibition in Patients With Congestive Heart Failure and in Healthy Control Subjects

• Published in: Journal of cardiac failure Vol. 19; no. 11; pp. 776 - 785
• Main Authors: Bech, J.N., Starklint, J., Bentzen, H., Nyvad, O., Pedersen, E.B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2013
• Subjects: Aged; aldosterone; Aldosterone - blood; ANP; Atrial Natriuretic Factor - blood; Blood Flow Velocity - drug effects; Blood Flow Velocity - physiology; Cardiovascular; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Female; Glomerular Filtration Rate - drug effects; Glomerular Filtration Rate - physiology; Heart Failure - blood; Heart Failure - drug therapy; Heart Failure - urine; Humans; Kidney - blood supply; Kidney - drug effects; Kidney - metabolism; Male; Middle Aged; NG-monomethyl-L-arginine; Nitric oxide; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - blood; Nitric Oxide - urine; omega-N-Methylarginine - pharmacology; omega-N-Methylarginine - therapeutic use; renal plasma flow; Vascular Resistance - drug effects; Vascular Resistance - physiology; NG-monomethyl-L-arginine; ANP; Nitric oxide; aldosterone; renal plasma flow; N G-monomethyl-L-arginine; N(G)-monomethyl-L-arginine
• ISSN: 1071-9164; 1532-8414; 1532-8414
• DOI: 10.1016/j.cardfail.2013.10.001

The significance of basal renal nitric oxide (NO) availability in the regulation of renal perfusion and sodium excretion in human congestive heart failure (CHF) has not been described previously. We studied the effects of acute systemic NO synthesis inhibition with NG-monomethyl-L-arginine (L-NMMA) in 12 patients with CHF and 10 healthy control subjects (CON) in a randomized placebo-controlled study. Effect parameters were renal plasma flow (RPF), renal vascular resistance (RVR), glomerular filtration rate (GFR), urine sodium excretion and plasma levels of vasoactive hormones. L-NMMA was associated with a significant decrease in RPF (CON-LNMMA: −13 ± 3% [P = .014]; CHF-LNMMA: −17 ± 7% [P = .017]) and a profound increase in RVR in both CHF and CON (CON-LNMMA: +26 ± 6% [P = .009]; CHF-LNMMA: +37 ± 70% [P = .005]). Significant decreases in sodium excretion were found in both CHF-LNMMA and CON-LNMMA. Relative changes from baseline were not statistically different between CHF-LNMMA and CON-LNMMA. After L-NMMA, RPF values correlated inversely with plasma aldosterone in CHF-LNMMA (P = .01). L-NMMA induced an increase in A-type natriuretic peptide (ANP) only in CHF-LNMMA (+18 ± 8%; P = .035), which correlated significantly with basal ANP levels (P = .034). There was no difference in the renal response to L-NMMA in CHF vs CON, suggesting that the impact of NO on renal perfusion and sodium excretion is maintained in stable CHF. We suggest that NO influences the release of ANP during high levels of atrial stretch in CHF.