Differential role of endothelial versus neuronal nitric oxide synthase in the regulation of coronary blood flow during pacing-induced increases in cardiac workload

Husain Shabeeh, Narbeh Melikian, Rafal Dworakowski, Barbara Casadei, Phil Chowienczyk, Ajay M. Shah*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Endothelial nitric oxide synthase (eNOS) was assumed to be the only source of nitric oxide (NO) involved in the regulation of human coronary blood flow (CBF). However, our recent first-in-human study using the neuronal NOS (nNOS)-selective inhibitor S-methyl-L-thiocitrulline (SMTC) showed that nNOS-derived NO also plays a role. In this study, we investigated the relative contribution of nNOS and eNOS to the CBF response to a pacing-induced increase in cardiac workload. Incremental right atrial pacing was undertaken in patients with angiographically normal coronary arteries during intracoronary infusion of saline vehicle and then either SMTC or N-G-monomethyl-L-arginine (L-NMMA; which inhibits both eNOS and nNOS). Intracoronary SMTC (0.625 mu mol/min) and L-NMMA (25 mu mol/min) reduced basal CBF to a similar extent (-19.2 +/- 3.2% and 25.0 +/- 2.7%, respectively; n = 10 per group). Pacing-induced increases in CBF were significantly blunted by L-NMMA (maximum CBF: 83.5 +/- 14.2 ml/min during saline vs. 61.6 +/- 9.5 ml/min during L-NMMA; P <0.01). By contrast, intracoronary SMTC had no effect on the maximum CBF during pacing (98.5 +/- 12.9 ml/min during saline vs. 102.1 +/- 16.6 ml/min during SMTC; P = not significant). L-NMMA also blunted the pacing-induced increase in coronary artery diameter (P <0.001 vs. saline), whereas SMTC had no effect. Our results confirm a role of nNOS in the regulation of basal CBF in humans but show that coronary vasodilation in response to a pacing-induced increase in cardiac workload is exclusively mediated by eNOS-derived NO.

Original languageEnglish
Article numberN/A
Pages (from-to)H1277-H1282
Number of pages6
JournalAMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume304
Issue number9
DOIs
Publication statusPublished - 1 May 2013

Keywords

  • coronary blood flow
  • endothelial nitric oxide synthase
  • neuronal nitric oxide synthase
  • pacing
  • vascular
  • IN-VIVO
  • VASOMOTOR RESPONSE
  • SKELETAL-MUSCLE
  • HUMAN HEART
  • ARTERIES
  • EXERCISE
  • ATHEROSCLEROSIS
  • BASAL
  • VASODILATION
  • CIRCULATION

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