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.

doi:10.1016/j.jash.2006.11.002

« Previous Next »Journal of the American Society of Hypertension
Volume 1, Issue 1 , Pages 45-55, January 2007

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

Masood Gilani, MD
- Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
- Current address: Bay Pines VA Hospital, St. Petersburg, Florida, USA
Daniel R. Kaiser, PhD
- Research Division, Saint Paul Heart Clinic, St. Paul, Minnesota, USA
- Current address: Medtronic, Minneapolis, Minneapolis, USA
Christopher W. Bratteli, MD
- Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
- Current address: University of Texas Southwestern Medical Center, Dallas, Texas, USA
Cheryl Alinder, LPN
- Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
Scott Rajala, BS
- Research Division, Saint Paul Heart Clinic, St. Paul, Minnesota, USA
Alan J. Bank, MD
- Research Division, Saint Paul Heart Clinic, St. Paul, Minnesota, USA
Jay N. Cohn, MD
- Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
- Dr. Jay N. Cohn is a founder and stockholder of Hypertension Diagnostics, Inc., the manufacturer of the CR2000 CV Profilor that was provided for use in this study.
- Corresponding author: Jay N. Cohn, MD, Cardiovascular Division, Mayo Mail Code 508, University of Minnesota Medical School, 420 Delaware Street, SE, Minneapolis, Minnesota 55455. Tel: 612-625-5646; fax: 612-624-2174.

Received 9 November 2006; accepted 10 November 2006.

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.

Keywords: Arteries, elasticity, nitric oxide, endothelium, norepinephrine