From the Department of Clinical Pharmacology, St Bartholomew's and
The Royal School of Medicine and Dentistry, London (P.F., A.J., N.B.); the
Department of Clinical Pharmacology, UMDS, St Thomas' Hospital, London
(B.J.K., P.J.C., J.M.R.); and the Rowett Research Institute, Aberdeen (E.M.),
UK.
Correspondence to Professor Nigel Benjamin, Department of Clinical Pharmacology, St Bartholomew's and The Royal School of Medicine and Dentistry, Charterhouse Square, London, EC1 M 6BQ, UK. E-mail n.benjamin{at}mds.qmw.ac.uk
Abstract—There is indirect
evidence for a gender difference in nitric oxide (NO) synthesis from
vascular endothelium. The aim of the present study
was to determine NO production more directly in healthy women
and men by the measurement of 15N nitrate excreted in urine
after the intravenous administration of
L-[15N]2-guanidino arginine.
Twenty-four healthy volunteers (13 men aged 22 to 40 years and 11 women
aged 23 to 42 years) participated in this study. No subjects were
receiving any medication. Women were studied between the 7th and 14th
days of their menstrual cycles. Arterial blood pressure was
measured oscillometrically, and 1.13 µmol
L-[15N]2 arginine was
administered intravenously after an overnight fast. Urine
was collected for the next 36 hours in separate 12-hour periods.
Urinary 15N/14N nitrate ratio was assessed by
dry combustion in an isotope ratio mass spectrometer. Mean 36-hour
urinary 15N nitrate excretion was greater in women than in
men (2111±139 versus 1682±87
© 1998 American Heart Association, Inc.
Scientific Contributions
Evidence for a Difference in Nitric Oxide Biosynthesis Between Healthy Women and Men
mol; P<0.05).
Furthermore, total urinary 15N nitrate excretion was
associated inversely with the mean arterial blood pressure
in the whole group of subjects (coefficient of correlation, 0.47;
P=0.022). The present data show that whole-body
production of NO is greater in healthy premenopausal women than
in men under ambulatory conditions. The cellular origin of NO measured
in this study is unknown, but differences in
endothelial production could underlie
differences in vascular function between men and women.
Key Words: endothelium-derived relaxing factor • arginine • nitrates • gender • adults
This article has been cited by other articles:
 |
|
 |
|
  J. C. Sullivan, J. L. Pardieck, K. A. Hyndman, and J. S. Pollock Renal NOS activity, expression, and localization in male and female spontaneously hypertensive rats Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2010; 298(1): R61 - R69. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Cifuentes, J. Bravo, M. Norambuena, S. Stegen, A. Ayavire, and J. Palacios Chronic Exposure to Arsenic in Tap Water Reduces Acetylcholine-induced Relaxation in the Aorta and Increases Oxidative Stress in Female Rats International Journal of Toxicology, November 1, 2009; 28(6): 534 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Baylis Sexual Dimorphism of the Aging Kidney: Role of Nitric Oxide Deficiency Physiology, June 1, 2008; 23(3): 142 - 150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. Patel and R. R. Arora Review: Endothelial dysfunction: A potential tool in gender related cardiovascular disease Therapeutic Advances in Cardiovascular Disease, April 1, 2008; 2(2): 89 - 100. [Abstract] [PDF]
|
|
|
|
 |
|
 J. U. Gonzales, B. C. Thompson, J. R. Thistlethwaite, A. J. Harper, and B. W. Scheuermann Forearm blood flow follows work rate during submaximal dynamic forearm exercise independent of sex J Appl Physiol, December 1, 2007; 103(6): 1950 - 1957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Ahmed, N. D.L. Fisher, and N. K. Hollenberg Gender and the Renal Nitric Oxide Synthase System in Healthy Humans Clin. J. Am. Soc. Nephrol., September 1, 2007; 2(5): 926 - 931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Baccari, S. Nistri, M. G. Vannucchi, F. Calamai, and D. Bani Reversal by relaxin of altered ileal spontaneous contractions in dystrophic (mdx) mice through a nitric oxide-mediated mechanism Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R662 - R668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Miller, G. R. Drummond, A. E. Mast, H. H.H.W. Schmidt, and C. G. Sobey Effect of Gender on NADPH-Oxidase Activity, Expression, and Function in the Cerebral Circulation: Role of Estrogen Stroke, July 1, 2007; 38(7): 2142 - 2149. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. K. Rana, P. A. Insel, S. H. Payne, K. Abel, E. Beutler, M. G. Ziegler, N. J. Schork, and D. T. O'Connor Population-Based Sample Reveals Gene-Gender Interactions in Blood Pressure in White Americans Hypertension, January 1, 2007; 49(1): 96 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. B. Berg Differences in decline in GFR with age between males and females. Reference data on clearances of inulin and PAH in potential kidney donors Nephrol. Dial. Transplant., September 1, 2006; 21(9): 2577 - 2582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S D Robinson, C A Ludlam, N A Boon, and D E Newby Phosphodiesterase type 5 inhibition does not reverse endothelial dysfunction in patients with coronary heart disease Heart, February 1, 2006; 92(2): 170 - 176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Page, H. Reich, J. Zhou, V. Lai, D. C. Cattran, J. W. Scholey, and J. A. Miller Endothelial Nitric Oxide Synthase Gene/Gender Interactions and the Renal Hemodynamic Response to Angiotensin II J. Am. Soc. Nephrol., October 1, 2005; 16(10): 3053 - 3060. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Khalil Sex Hormones as Potential Modulators of Vascular Function in Hypertension Hypertension, August 1, 2005; 46(2): 249 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V L Clifton, R Crompton, M A Read, P G Gibson, R Smith, and I M R Wright Microvascular effects of corticotropin-releasing hormone in human skin vary in relation to estrogen concentration during the menstrual cycle J. Endocrinol., July 1, 2005; 186(1): 69 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. C. Luiking, M. M. Hallemeesch, Y.L.J. Vissers, W. H. Lamers, and N.E.P. Deutz In Vivo Whole Body and Organ Arginine Metabolism During Endotoxemia (Sepsis) Is Dependent on Mouse Strain and Gender J. Nutr., October 1, 2004; 134(10): 2768S - 2774S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.E.S. Miner, A. Al-Hesayen, S. Kelly, T. Benson, J.J. Thiessen, V.R. Young, and J.D. Parker L-Arginine Transport in the Human Coronary and Peripheral Circulation Circulation, March 16, 2004; 109(10): 1278 - 1283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Orshal and R. A. Khalil Gender, sex hormones, and vascular tone Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R233 - R249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Chatrath, K. L. Ronningen, P. LaBreche, S. R. Severson, M. Jayachandran, M. P. Bracamonte, and V. M. Miller Effect of puberty on coronary arteries from female pigs J Appl Physiol, October 1, 2003; 95(4): 1672 - 1680. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Attia, R. Goldschmeding, M. A. Attia, P. Boer, H. A. Koomans, and J. A. Joles Male gender increases sensitivity to renal injury in response to cholesterol loading Am J Physiol Renal Physiol, April 1, 2003; 284(4): F718 - F726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Persu, M. S. Stoenoiu, T. Messiaen, S. Davila, C. Robino, O. El-Khattabi, M. Mourad, S. Horie, O. Feron, J. -L. Balligand, et al. Modifier effect of ENOS in autosomal dominant polycystic kidney disease Hum. Mol. Genet., February 1, 2002; 11(3): 229 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Sullivan and C. A. Davison Effect of age on electrical field stimulation (EFS)-induced endothelium-dependent vasodilation in male and female rats Cardiovasc Res, April 1, 2001; 50(1): 137 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. KISSOON, L. J. DUCKWORTH, K. V. BLAKE, S. P. MURPHY, C. L. TAYLOR, and P. E. SILKOFF FENO: Relationship to Exhalation Rates and Online versus Bag Collection in Healthy Adolescents Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): 539 - 545. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. O. Steinberg, G. Paradisi, J. Cronin, K. Crowde, A. Hempfling, G. Hook, and A. D. Baron Type II Diabetes Abrogates Sex Differences in Endothelial Function in Premenopausal Women Circulation, May 2, 2000; 101(17): 2040 - 2046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Majmudar, S. C. Robson, and G. A. Ford Effects of the Menopause, Gender, and Estrogen Replacement Therapy on Vascular Nitric Oxide Activity J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1577 - 1583. [Abstract] [Full Text]
|
|
|
|
|
|
C. S. Hayward, R. P. Kelly, and P. Collins The roles of gender, the menopause and hormone replacement on cardiovascular function Cardiovasc Res, April 1, 2000; 46(1): 28 - 49. [Full Text] [PDF]
|
|