Role of nitric oxide deficiency and its detection as a risk factor in pre-hypertension

Masood Gilani, Daniel R. Kaiser, Christopher W. Bratteli, Cheryl Alinder, Scott Rajala, Alan J. Bank, Jay N. Cohn

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Systemic inhibition of nitric oxide (NO) synthesis raises blood pressure, and endothelial dysfunction with reduced NO bioactivity is a precursor of atherosclerosis. Pre-hypertensive blood pressures place patients at increased risk for cardiovascular morbid events. Whether NO deficiency contributes to this increased risk has not been explored. Constitutive NO release was inhibited by infusion of the substituted arginine NG-nitro-L-arginine-methyl ester (L-NAME) in 10 normal volunteers. Hemodynamics, radial artery pulse contour analysis, brachial artery ultrasound, and aortic pulse wave velocity were monitored as well as plasma neurohormone levels. A modest rise in blood pressure within the normotensive range (113/65 to 124/77 mm Hg, P < .01) was accompanied by a rise in estimated systemic vascular resistance (1193 to 1514 dyne-sec-cm-5, P < .001). Pulse contour analysis revealed a fall to abnormal levels in systemic small artery elasticity (diastolic decay) (9.8 to 6.4 ml/mm Hg, P < .001) and a less consistent but significant increase in the second pressure peak in systole (P < .05). Large artery elasticity index, brachial artery caliber, and brachial artery compliance were unchanged. Flow-mediated brachial artery dilation was blunted slightly (5.29% to 4.47%, P = .06), and aortic pulse wave velocity increased slightly but significantly (8.25 to 8.98 m/s, P = .04), probably as a result of the rise in pressure. The magnitude of effect of L-NAME on small artery elasticity (-31.2% ± 18.4%) was significantly greater and more consistent than its effect on other vascular measurements. Circulating neurohormonal vasoconstrictor levels fell or were unchanged after L-NAME, and a significant reduction in plasma norepinephrine was closely inversely correlated with the rise in blood pressure. Nitroglycerin infusion in 4 additional subjects produced selective relaxation in small arteries, whereas norepinephrine constricted both small and large arteries. A hemodynamic state consistent with pre-hypertension was induced by NO synthase inhibition in normal volunteers. Reduction in small artery compliance was a sensitive marker for this induced endothelial dysfunction and may serve as a useful marker for pre-hypertensive patients at risk for cardiovascular morbid events.

Original languageEnglish (US)
Pages (from-to)45-55
Number of pages11
JournalJournal of the American Society of Hypertension
Volume1
Issue number1
DOIs
StatePublished - Jan 1 2007

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Prehypertension
Nitric Oxide
Brachial Artery
Arteries
NG-Nitroarginine Methyl Ester
Elasticity
Blood Pressure
Pulse Wave Analysis
Compliance
Pulse
Norepinephrine
Healthy Volunteers
Hemodynamics
Pressure
Radial Artery
Systole
Nitroglycerin
Vasoconstrictor Agents
Nitric Oxide Synthase
Vascular Resistance

Keywords

  • Arteries
  • elasticity
  • endothelium
  • nitric oxide
  • norepinephrine

Cite this

Role of nitric oxide deficiency and its detection as a risk factor in pre-hypertension. / Gilani, Masood; Kaiser, Daniel R.; Bratteli, Christopher W.; Alinder, Cheryl; Rajala, Scott; Bank, Alan J.; Cohn, Jay N.

In: Journal of the American Society of Hypertension, Vol. 1, No. 1, 01.01.2007, p. 45-55.

Research output: Contribution to journalArticle

Gilani, Masood ; Kaiser, Daniel R. ; Bratteli, Christopher W. ; Alinder, Cheryl ; Rajala, Scott ; Bank, Alan J. ; Cohn, Jay N. / Role of nitric oxide deficiency and its detection as a risk factor in pre-hypertension. In: Journal of the American Society of Hypertension. 2007 ; Vol. 1, No. 1. pp. 45-55.
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