Blood Pressure in Healthy Humans is Regulated by Neuronal NO Synthase

Husain Shabeeh, Sitara Khan, Benyu Jiang, Sally Brett, Narbeh Melikian, Barbara Casadei, Philip J. Chowienczyk, Ajay M. Shah*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)
172 Downloads (Pure)

Abstract

NO is physiologically generated by endothelial and neuronal NO synthase (nNOS) isoforms. Although nNOS was first identified in brain, it is expressed in other tissues, including perivascular nerves, cardiac and skeletal muscle. Increasing experimental evidence suggests that nNOS has important effects on cardiovascular function, but its composite effects on systemic hemodynamics in humans are unknown. We undertook the first human study to assess the physiological effects of systemic nNOS inhibition on basal hemodynamics. Seventeen healthy normotensive men aged 24±4 years received acute intravenous infusions of an nNOS-selective inhibitor, S-methyl-l-thiocitrulline, and placebo on separate occasions. An initial dose-escalation study showed that S-methyl-l-thiocitrulline (0.1-3.0 μmol/kg) induced dose-dependent changes in systemic hemodynamics. The highest dose of S-methyl-l-thiocitrulline (3.0 μmol/kg over 10 minutes) significantly increased systemic vascular resistance (+42±6%) and diastolic blood pressure (67±1 to 77±3 mm Hg) when compared with placebo (both P

Original languageEnglish
Pages (from-to)970-976
Number of pages7
JournalHypertension
Volume69
Issue number5
Early online date6 Mar 2017
DOIs
Publication statusPublished - 1 May 2017

Keywords

  • blood pressure
  • brain
  • humans
  • nitric oxide
  • stroke

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