This Article Abstract Full Text (PDF) All Versions of this Article: 42/5/915    most recent 01.HYP.0000092882.65699.19v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stewart, A. D. Articles by Chowienczyk, P. J. Search for Related Content PubMed PubMed Citation Articles by Stewart, A. D. Articles by Chowienczyk, P. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB NITRIC OXIDE Related Collections Endothelium/vascular type/nitric oxide

(Hypertension. 2003;42:915.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Effects of Inhibition of Basal Nitric Oxide Synthesis on Carotid-Femoral Pulse Wave Velocity and Augmentation Index in Humans

Andrew D. Stewart; Sandrine C. Millasseau; Mark T. Kearney; James M. Ritter; Philip J. Chowienczyk

From the Department of Clinical Pharmacology, St Thomas’ Hospital (A.D.S., S.C.M., J.M.R., P.J.C.), and the Department of Cardiology, King’s College Hospital (M.T.K.), King’s College, London, UK.

Correspondence to Dr Philip J. Chowienczyk, Department of Clinical Pharmacology, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH UK. E-mail phil.chowienczyk{at}kcl.ac.uk

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Aortic stiffness, as measured by carotid-femoral pulse wave velocity (PWV), is a powerful, independent predictor of vascular risk. PWV in muscular arteries is influenced by basal nitric oxide (NO) release. It is not known whether NO also influences carotid-femoral PWV. We examined the effects of an NO synthase inhibitor, N^G-monomethyl-L-arginine (L-NMMA), on carotid-femoral PWV and aortic augmentation index (AIx, an indirect measure of arterial stiffness). To control for effects of L-NMMA on distending pressure, we used doses of norepinephrine and dobutamine that caused similar changes in mean arterial blood pressure (MAP). Healthy men (32 to 48 years old, n=8) were studied on 4 occasions and received, in random order, vehicle, L-NMMA (3 mg · kg^-1 by intravenous bolus followed by 3 mg · kg^-1 · h^-1), norepinephrine (50 ng · kg^-1 · min^-1), and dobutamine (2.5 to 10 µg · kg^-1 · min^-1), each for 30 minutes. PWV and AIx were measured by carotid-femoral PWV and radial tonometry, respectively. L-NMMA and norepinephrine increased MAP by 7.8±1.7 and 9.7±2.1 mm Hg, respectively (each P<0.05 vs vehicle) and increased PWV by 0.7±0.2 and 1.0±0.3 m · s^-1 (each P<0.01 vs vehicle). Dobutamine, at doses that produced a similar increase in MAP (9.6±2.9 mm Hg), increased PWV by 0.8±0.2 m · s^-1 (P<0.01 vs vehicle). Changes in PWV caused by the 3 pressor agents were closely correlated with changes in MAP (R>0.99, P<0.0001). L-NMMA and norepinephrine increased AIx, but dobutamine decreased AIx (P<0.01 vs norepinephrine and L-NMMA). Effects of inhibition of basal NO release on carotid-femoral PWV can be explained by the change in MAP that this causes rather than any specific effect of NO inhibition within the aorta.

Key Words: aorta • elasticity • endothelium • nitric oxide • nitric oxide synthase

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Carotid-femoral pulse wave velocity (PWV), a measure of aortic stiffness,¹ is a powerful, independent predictor of cardiovascular events and mortality.^2–4 Aortic stiffening increases peak systolic pressure at the aortic root as a result of diminished systemic compliance and early return of pressure waves reflected from the periphery.^5,6 This provides a possible mechanism for the increased event rate and mortality associated with aortic stiffening. In addition, carotid-femoral PWV might serve as an integrated measure of the impact of cardiovascular risk factors on age-related changes in aortic structure.^4,7,8 In muscular arteries, stiffness is influenced by mean arterial blood pressure (MAP, a determinant of transmural distending pressure) and by the tone of arterial smooth muscle (which influences the elastic properties of the arterial wall). In the ovine iliac artery, basal release of nitric oxide (NO) contributes to the functional regulation of stiffness.⁹

The human aorta is rich in elastin, and with advancing age, increasing relative amounts of collagen, but it also contain vascular smooth muscle, especially in the abdomen.¹⁰ The extent to which aortic stiffness is influenced by vascular tone and in particular, by basal NO, has not previously been examined in the human aorta. The purpose of the present study was to investigate the functional regulation of central arteries in humans as measured by carotid-femoral PWV. We examined the influence of basal NO synthesis with the NO synthase inhibitor N^G-monomethyl-L-arginine (L-NMMA). We used norepinephrine and dobutamine to control for effects of L-NMMA on MAP. In addition to PWV, we also measured aortic augmentation index (AIx), an indirect index of vascular stiffness derived from the contour of the aortic pressure waveform,^5,11 to determine whether changes in AIx occurred in parallel with those of PWV.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Subjects were healthy, male volunteers (n=8; mean age, 40 years; range, 32 to 48 years). All were normotensive and normocholesterolemic (mean±SD total cholesterol, 5.1±0.4 mmol/L) and had normal renal function (serum creatinine, 102±14 µmol/L). No subject had a history of cardiovascular disease, and none was taking prescription or nonprescription drugs or vitamins. Subjects were studied on 4 separate occasions, each separated by at least 6 days. They received L-NMMA, norepinephrine, dobutamine, and saline vehicle in random order on the different study days. One subject was not available for the dobutamine study. The study was approved by the local Research Ethics Committee, and written, informed consent was obtained from each subject. Measurements were performed with subjects supine in a quiet, temperature-controlled (22°C to 24°C) environment after at least 15 minutes of rest. PWV was determined by electrocardiograph-gated carotid-femoral applanation tonometry (Millar Instruments) with available software (Sphygmocor version 6.3, Atcor). Three successive recordings were obtained, and measurements were repeated when the waveform(s) did not pass the automatic quality controls specified by the Sphygmocor software. Brachial artery blood pressure was measured in triplicate with an oscillometric device (Omron 705CP, Omron). AIx was derived from radial-artery waveforms obtained from the right radial artery and analyzed by the radial-to-aortic transfer function in the Sphygmocor pulse-wave analysis software to estimate aortic AIx.

After venous cannulation and 15 minutes of supine rest, 0.9% saline vehicle was infused and baseline hemodynamic measurements were obtained for 30 minutes. Subjects then received either a further infusion of saline vehicle or 1 of L-NMMA, norepinephrine, or dobutamine, depending on the study day. L-NMMA (Clinalfa) was given as a 3 mg · kg^-1 bolus over 5 minutes, followed by infusion at 3 mg · kg^-1 · h^-1 for 30 minutes and norepinephrine (Abbot) infused at 50 ng · kg^-1 · min^-1 for 30 minutes. The dose of L-NMMA was based on that used in previous studies.^12–15 The dose of norepinephrine was estimated from results of pilot studies to give a similar increase in MAP. Dobutamine (Phoenix Pharma) was infused at 2.5 µg · kg^-1 · min^-1 for 15 minutes and at 5 µg · kg^-1 · min^-1 for 15 minutes. Five subjects received an additional 15-minute infusion of dobutamine at 10 µg · kg^-1 · min^-1. PWV and AIx were recorded throughout. Hemodynamic measurements were repeated at 10-minute intervals during infusion of saline, L-NMMA, and norepinephrine and at 5-minute intervals during infusion of dobutamine. MAP and PWV remained approximately constant throughout the infusion of each dose of the vasoactive drugs, and mean values were used for analysis.

Analysis
Results were summarized as mean±SE. PWV and AIx responses to the dose of dobutamine that produced an increase in MAP closest to that produced by L-NMMA in that subject were used for the primary analysis. Differences between responses to the vasoactive drugs relative to saline vehicle were sought by repeated-measures ANOVA. In addition, the influence of the drug on PWV, with all doses of dobutamine, with the change in MAP incorporated as a covariate was examined by a general linear model (SPSS version 11.5). P<0.05 was considered significant, and all tests were 2 tailed.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Hemodynamic measurements during infusion of saline and vasopressor drugs are summarized in the Table. During infusion of saline, MAP did not change significantly relative to baseline (-2.8±1.9 mm Hg), although there was a tendency for blood pressure to fall during the course of the study. Analysis of responses to drugs was performed relative to saline vehicle. L-NMMA and norepinephrine increased MAP by a similar extent (7.8±1.7 and 9.7±2.1 mm Hg, respectively; each P<0.05; Figure 1). For doses of dobutamine that produced a similar increase in MAP (9.6±2.9 mm Hg), L-NMMA, norepinephrine, and dobutamine all increased PWV (0.7±0.2, 1.0±0.3, and 0.8±0.2 m · s^-1 respectively; each P<0.01). There was no significant difference between the effects of L-NMMA, norepinephrine, and dobutamine on PWV. When all doses of dobutamine were included, with the change in MAP incorporated as a covariate, there was no significant effect of drug class on PWV. By contrast, there was a close association between change in PWV and change in MAP (R>0.99, P<0.0001, for mean change in PWV vs mean change in MAP for each class of drug; Figure 2). L-NMMA reduced heart rate (-6.1±1.1 beats per minute [bpm], P<0.01), whereas norepinephrine and dobutamine (2.5 to 5 µg · kg^-1 · min^-1) did not. L-NMMA and norepinephrine increased AIx relative to saline (10.2±1.9% and 13.2±4.4%, respectively, relative to saline; each P<0.05), whereas dobutamine did not (-4.4±3.2% for equipressor doses; P=NS). The effects of L-NMMA and norepinephrine on AIx differed from that of dobutamine (each P<0.01).

View this table: [in this window] [in a new window]   Effect of Saline, L-NMMA, Norepinephrine (NE), and Dobutamine (DOB) on Hemodynamic Measurements

View larger version (12K): [in this window] [in a new window]   Figure 1. Changes from baseline (relative to saline vehicle) in MAP (MAP), aortic PWV (PWV), and aortic AIx (AIx) during intravenous infusion of L-NMMA (3 mg · kg-1 bolus; 3 mg · kg-1 · h-1), norepinephrine (NE, 50 ng · kg-1 · min-1), and equipressor doses of dobutamine (DOB, 2.5 to 5 µg · g-1 · min-1). *P<0.05, **P<0.01.

View larger version (11K): [in this window] [in a new window]   Figure 2. Relation between mean change in PWV (PWV) vs mean change in MAP (MAP) during dobutamine (2.5 µg · kg-1 · min-1, , dobutamine (5 µg · kg-1 · min-1, ) dobutamine (10 µg · kg-1 · min-1, O), L-NMMA (3 mg · kg-1 bolus; 3 mg · kg-1 · h-1, ), and norepinephrine (50 ng · kg-1 · min-1, ). R>0.99, P<0.0001 (linear regression). The dotted line shows the best-fit second-order polynomial.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
Stiffness of muscular arteries is strongly influenced by transmural pressure and hence by MAP (because pressure on the adventitial surface of the artery is usually negligible).^16,17 In the brachial artery, transmural pressure can be modulated by the application of an external blood pressure cuff, thus allowing effects of vasoactive drugs to be determined independently from the effects on MAP.¹⁷ Studies with this technique show that, independent of transmural pressure, brachial artery elasticity is sensitive to changes in smooth muscle tone induced by NO: the NO donor nitroglycerine decreases stiffness,¹⁷ and inhibition of basal NO synthesis by L-NMMA increases stiffness.¹⁸ Direct infusion of L-NMMA into the sheep iliac artery increased the stiffness of this musculoelastic artery without a significant effect on MAP,⁹ suggesting that this artery is also influenced by basal NO release.

Less is known regarding the influence of vascular tone on the functional regulation of large arteries such as the thoracic aorta. This is important, because there are marked differences between muscular and elastic arteries with respect to aging and the association between stiffness and cardiovascular risk.^5,19 Muscular arteries show little increase in stiffness with age in contrast to elastic arteries.²⁰ Age-related stiffening of elastic arteries, particularly the aorta, is accelerated in the presence of risk factors for cardiovascular disease.^7,8 Aortic stiffness, estimated from carotid-femoral PWV, by contrast with the stiffness of muscular arteries, is highly predictive of cardiovascular events and mortality.^2–4 In the present study, we examined the effects of inhibition of basal NO synthesis on carotid-femoral PWV in healthy men with the use of norepinephrine and dobutamine to control for the effects on MAP.

L-NMMA increased blood pressure, as expected.^12–15 L-NMMA increased carotid-femoral PWV equivalent to 8 years of aging, as estimated from the relation found by Avolio et al.²¹ However, the increase in carotid-femoral PWV was similar to that produced by equipressor (MAP) doses of norepinephrine and dobutamine. Norepinephrine increases blood pressure mainly through an increase in peripheral resistance, whereas dobutamine, a ß₁-selective agonist, acts mainly as a positive inotrope and dilates rather than constricts arterial smooth muscle.²² An increase in PWV in response to norepinephrine could be caused by an increase in smooth muscle tone in the aorta. However, the increase in PWV in response to norepinephrine was similar to that obtained with dobutamine, which does not constrict vascular smooth muscle. The similarity of the PWV response to the vasopressor agents with diverse mechanisms on the heart and vasculature and the close correlation between change in PWV and change in MAP, irrespective of the drug used, strongly suggest that MAP is the most important determinant of short-term changes in carotid-femoral PWV.

An additional aim of the present study was to examine the effects of NO synthase inhibition on AIx. AIx has been used as an index of arterial stiffness but is also influenced by ventricular ejection and by the tone of muscular arteries, which influences pressure wave reflection.⁵ In the present study, we observed a disassociation between the effects of vasopressor drugs on AIx and carotid-femoral PWV. In agreement with previous studies, L-NMMA and norepinephrine increased AIx.^23,24 By contrast and despite a similar increase in MAP and PWV to that produced by L-NMMA and norepinephrine, dobutamine decreased AIx. This novel finding is not entirely unexpected for an arterial vasodilator in the context of earlier observations that AIx can change independently of aortic PWV,²⁵ and this reinforces the need for caution in the interpretation of AIx during pharmacologic interventions, as stressed by O’Rourke et al.⁵ The different effect of dobutamine on AIx compared with the other 2 pressors could have resulted from a relaxant effect of dobutamine on muscular arteries, thereby reducing pressure wave reflection. An alternative or additional explanation could be increased myocardial contractility, leading to a more rapid rise in aortic pressure in systole. This would increase separation of direct and reflected components of the pressure wave and decrease augmentation of early systolic pressure by pressure wave reflection.

Limitations of the Study
There are several limitations to this study. Carotid-femoral PWV reflects vascular stiffness in both the aorta and iliac artery. The iliac artery is more muscular than the aorta, and it is possible that these arteries differ in the extent to which smooth muscle tone influences stiffness. We cannot exclude an influence of endogenous NO release on local stiffness in the iliac artery if this were much less than the passive influence of distending pressure in the aorta. To detect this would require local administration of L-NMMA, as described in sheep.⁹ The importance of carotid-femoral PWV is that it is easily measured and is strongly predictive of coronary artery disease events in humans.^2,3

In addition, L-NMMA, norepinephrine, and dobutamine influence systolic blood pressure, diastolic blood pressure, and MAP differently. Systolic blood pressure is determined mainly by stroke volume and aortic stiffness.²⁶ Dobutamine, a positive inotrope, is expected to increase stroke volume and hence, systolic blood pressure more than norepinephrine and L-NMMA (which is a negative inotrope). Given their differing modes of action, it was not possible to cause similar changes in systolic, diastolic, and mean arterial pressure with all 3 agents. Doses of L-NMMA, norepinephrine, and dobutamine were therefore chosen to give similar effects on MAP, a measure of the mean distending pressure throughout the cardiac cycle.

Last, there was a difference in the heart rate response to L-NMMA and the other pressor drugs of 6 bpm. PWV exhibits some dependence on heart rate,²⁷ but this occurs only at heart rates >70 bpm, when a change in heart rate of 6 bpm would produce a change in PWV of <0.3 m · s^-1. The average heart rate during drug infusions ranged from 51 to 61 bpm. It is unlikely, therefore, that the difference in heart rate for the different drugs had a substantial effect on PWV.

Perspectives
In conclusion, short-term inhibition of basal NO release has an effect on carotid-femoral PWV similar to that of 8 years of vascular aging. This is similar to the effects of equipressor (for MAP) doses of norepinephrine and dobutamine, suggesting that the change in MAP accounts for these short-term changes in PWV. There is no evidence of any additional, specific effect of NO inhibition on carotid-femoral PWV. There is a disassociation between the effects of vasoactive drugs on PWV and AIx, consistent with their differing actions on the heart and vascular smooth muscle.

	Acknowledgments

 
This work was supported by a grant from the Charitable Foundation of Guy’s and St Thomas’ Hospital.

Received July 11, 2003; first decision July 25, 2003; accepted August 18, 2003.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Bramwell JC, Hill AV. Velocity of transmission of the pulse and elasticity of arteries. Lancet. 1922; 1: 891–892.

2. Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME. Impact of aortic stiffness on survival in end-stage renal disease. Circulation. 1999; 99: 2434–2439.[Abstract/Free Full Text]

3. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, Ducimetiere P, Benetos A. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001; 37: 1236–1241.[Abstract/Free Full Text]

4. Cruickshank K, Riste L, Anderson SG, Wright JS, Dunn G, Gosling RG. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation. 2002; 106: 2085–2090.[Abstract/Free Full Text]

5. O’Rourke MF, Staessen JA, Vlachopoulos C, Duprez D, Plante GE. Clinical applications of arterial stiffness: definitions and reference values. Am J Hypertens. 2002; 15: 426–444.[CrossRef][Medline] [Order article via Infotrieve]

6. Safar ME, Levy BI, Struijker-Boudier H. Current perspectives on arterial stiffness and pulse pressure in hypertension and cardiovascular diseases. Circulation. 2003; 107: 2864–2869.[Free Full Text]

7. Lehmann ED, Hopkins KD, Rawesh A, Joseph RC, Kongola K, Coppack SW, Gosling RG. Relation between number of cardiovascular risk factors/events and noninvasive Doppler ultrasound assessments of aortic compliance. Hypertension. 1998; 32: 565–569.[Abstract/Free Full Text]

8. Blacher J, Asmar R, Djane S, London GM, Safar ME. Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension. 1999; 33: 1111–1117.[Abstract/Free Full Text]

9. Wilkinson IB, Qasem A, McEniery CM, Webb DJ, Avolio AP, Cockcroft JR. Nitric oxide regulates local arterial distensibility in vivo. Circulation. 2002; 105: 213–217.[Abstract/Free Full Text]

10. Faber M, Moller-Hou G. The human aorta, part V: collagen and elastin in the normal and hypertensive aorta. Acta Pathol Microbiol Scand. 1952; 31: 377–382.[Medline] [Order article via Infotrieve]

11. O’Rourke MF, Mancia G. Arterial stiffness. J Hypertens. 1999; 17: 1–4.[Medline] [Order article via Infotrieve]

12. Brett SE, Cockcroft JR, Mant TGK, Ritter JM, Chowienczyk PJ. Haemodynamic effects of inhibition of nitric oxide synthase and of L-arginine at rest and during exercise. J Hypertens. 1998; 16: 429–435.[CrossRef][Medline] [Order article via Infotrieve]

13. Chowienczyk PJ, Kelly RP, MacCallum H, Millasseau SC, Andersson TLG, Gosling RG, Ritter JM, Änggård EE. Photoplethysmographic assessment of pulse wave reflection: blunted endothelium-dependent response to ß₂-adrenergic vasodilation in type II diabetes. J Am Coll Cardiol. 1999; 34: 2007–2014.[Abstract/Free Full Text]

14. Haynes WG, Noon JP, Walker BR, Webb DJ. Inhibition of nitric oxide synthesis increases blood pressure in healthy humans. J Hypertens. 1993; 11: 1375–1380.[Medline] [Order article via Infotrieve]

15. Haynes WG, Hand MF, Dockrell ME, Eadington DW, Lee MR, Hussein Z, Benjamin N, Webb DJ. Physiological role of nitric oxide in regulation of renal function in humans. Am J Physiol. 1997; 272: F364–F371.[Medline] [Order article via Infotrieve]

16. Bank AJ, Wang H, Holte JE, Mullen K, Shammas R, Kubo SH. Contribution of collagen, elastin, and smooth muscle to in vivo human brachial artery wall stress and elastic modulus. Circulation. 1996; 94: 3263–3270.[Abstract/Free Full Text]

17. Bank AJ, Kaiser DR, Rajala S, Cheng A. In vivo human brachial artery elastic mechanics: effects of smooth muscle relaxation. Circulation. 1999; 100: 41–47.[Abstract/Free Full Text]

18. Kinlay S, Creager MA, Fukumoto M, Hikita H, Fang JC, Selwyn AP, Ganz P. Endothelium-derived nitric oxide regulates arterial elasticity in human arteries in vivo. Hypertension. 2001; 38: 1049–1053.[Abstract/Free Full Text]

19. Heijden-Spek JJ, Staessen JA, Fagard RH, Hoeks AP, Boudier HA, van Bortel LM. Effect of age on brachial artery wall properties differs from the aorta and is gender dependent: a population study. Hypertension. 2000; 35: 637–642.[Abstract/Free Full Text]

20. Avolio AP, Deng FQ, Li WQ, Luo YF, Huang ZD, Xing LF, O’Rourke MF. Effects of aging on arterial distensibility in populations with high and low prevalence of hypertension: comparison between urban and rural communities in China. Circulation. 1985; 71: 202–210.[Abstract/Free Full Text]

21. Avolio AP, Chen SG, Wang RP, Zhang CL, Li MF, O’Rourke MF. Effects of aging on changing arterial compliance and left ventricular load in a northern Chinese urban community. Circulation. 1983; 68: 50–58.[Abstract/Free Full Text]

22. Nichols WW, O’Rourke MF. Therapeutic and monitoring strategies. In: McDonald’s Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles. London, UK: Arnold; 1998: 426.

23. Wilkinson IB, MacCallum H, Cockcroft JR, Webb DJ. Inhibition of basal nitric oxide synthesis increases aortic augmentation index and pulse wave velocity in vivo. Br J Clin Pharmacol. 2002; 53: 189–192.[CrossRef][Medline] [Order article via Infotrieve]

24. Wilkinson IB, MacCallum H, Hupperetz PC, van Thoor CJ, Cockcroft JR, Webb DJ. Changes in the derived central pressure waveform and pulse pressure in response to angiotensin II and noradrenaline in man. J Physiol. 2001; 530: 541–550.[Abstract/Free Full Text]

25. Kelly RP, Millasseau SC, Ritter JM, Chowienczyk PJ. Vasoactive drugs influence aortic augmentation index independently of pulse wave velocity in healthy men. Hypertension. 2001; 37: 1429–1433.[Abstract/Free Full Text]

26. Stergiopulos N, Westerhof N. Determinants of pulse pressure. Hypertension. 1998; 32: 556–559.[Abstract/Free Full Text]

27. Lantelme P, Mestre C, Lievre M, Gressard A, Milon H. Heart rate: an important confounder of pulse wave velocity assessment. Hypertension. 2002; 39: 1083–1087.[Abstract/Free Full Text]

This article has been cited by other articles:

				S. V. Getov, R. W. Lee, F. Dockery, and C. Rajkumar Androgens, ageing and vascular function Age Ageing, July 1, 2008; 37(4): 361 - 363. [Full Text] [PDF]

				D. J. Penny, J. P. Mynard, and J. J. Smolich Aortic wave intensity analysis of ventricular-vascular interaction during incremental dobutamine infusion in adult sheep Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H481 - H489. [Abstract] [Full Text] [PDF]

				N Bjarnegard, C Bengtsson, J Brodszki, G Sturfelt, O Nived, and T Lanne Increased aortic pulse wave velocity in middle aged women with systemic lupus erythematosus Lupus, October 1, 2006; 15(10): 644 - 650. [Abstract] [PDF]

				A. D. Stewart, B. Jiang, S. C. Millasseau, J. M. Ritter, and P. J. Chowienczyk Acute Reduction of Blood Pressure by Nitroglycerin Does Not Normalize Large Artery Stiffness in Essential Hypertension Hypertension, September 1, 2006; 48(3): 404 - 410. [Abstract] [Full Text] [PDF]

				J. Bellien, R. Joannides, M. Iacob, P. Arnaud, and C. Thuillez Calcium-Activated Potassium Channels and NO Regulate Human Peripheral Conduit Artery Mechanics Hypertension, July 1, 2005; 46(1): 210 - 216. [Abstract] [Full Text] [PDF]

				M. Schmitt, A. Avolio, A. Qasem, C. M. McEniery, M. Butlin, I. B. Wilkinson, and J. R. Cockcroft Basal NO Locally Modulates Human Iliac Artery Function In Vivo Hypertension, July 1, 2005; 46(1): 227 - 231. [Abstract] [Full Text] [PDF]

				J. A. Chirinos, J. P. Zambrano, S. Chakko, A. Veerani, A. Schob, H. J. Willens, G. Perez, and A. J. Mendez Aortic Pressure Augmentation Predicts Adverse Cardiovascular Events in Patients With Established Coronary Artery Disease Hypertension, May 1, 2005; 45(5): 980 - 985. [Abstract] [Full Text] [PDF]

				S. C. Millasseau, A. D. Stewart, S. J. Patel, S. R. Redwood, and P. J. Chowienczyk Evaluation of Carotid-Femoral Pulse Wave Velocity: Influence of Timing Algorithm and Heart Rate Hypertension, February 1, 2005; 45(2): 222 - 226. [Abstract] [Full Text] [PDF]

				J. Sugawara, S. Maeda, T. Otsuki, T. Tanabe, R. Ajisaka, and M. Matsuda Effects of nitric oxide synthase inhibitor on decrease in peripheral arterial stiffness with acute low-intensity aerobic exercise Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2666 - H2669. [Abstract] [Full Text] [PDF]

				I. B. Wilkinson, S. S. Franklin, and J. R. Cockcroft Nitric Oxide and the Regulation of Large Artery Stiffness: From Physiology to Pharmacology Hypertension, August 1, 2004; 44(2): 112 - 116. [Full Text] [PDF]

				A. M. Dart, C. D. Gatzka, J. D. Cameron, B. A. Kingwell, Y.-L. Liang, K. L. Berry, C. M. Reid, and G. L. Jennings Large Artery Stiffness Is Not Related to Plasma Cholesterol in Older Subjects with Hypertension Arterioscler Thromb Vasc Biol, May 1, 2004; 24(5): 962 - 968. [Abstract] [Full Text]

				K. Mather and R. Lewanczuk Measurement of Arterial Stiffness in Diabetes: A cautionary tale Diabetes Care, March 1, 2004; 27(3): 831 - 833. [Full Text] [PDF]

This Article Abstract Full Text (PDF) All Versions of this Article: 42/5/915    most recent 01.HYP.0000092882.65699.19v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stewart, A. D. Articles by Chowienczyk, P. J. Search for Related Content PubMed PubMed Citation Articles by Stewart, A. D. Articles by Chowienczyk, P. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB NITRIC OXIDE Related Collections Endothelium/vascular type/nitric oxide