Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Lack of changes in carotid artery compliance with systemic nitric oxide synthase inhibition

Abstract

Proximal large elastic arteries (ascending aorta and carotid artery) have an important role in buffering the pulsatile pressure generated from the left ventricle, which forwards continuous peripheral blood flow and protects the brain microcirculation from end-organ damage. Although compliance of distal conduit arteries (extremities’ arteries) is attenuated by the nitric oxide synthase (NOS) inhibition, it is yet unknown whether compliance of proximal elastic arteries changes by the systemic NOS inhibition. To address this question, we measured central artery compliance in 17 young adults (26±1 years) who underwent intravenous infusions of NG-monomethyl-L-arginine (L-NMMA) or saline (placebo) on separate days. Following the systemic NOS inhibition, the mean arterial pressure (MAP), total peripheral resistance and aortic augmentation index were significantly increased. However, carotid artery compliance was not affected significantly (from 0.10±0.01 to 0.11±0.01 mm2 per mmHg) and the β-stiffness index (an index of arterial compliance adjusted for the distending pressure) tended to decrease (from 6.63±0.35 to 6.06±0.42 a.u., P=0.07). These parameters were not altered with saline infusion. Changes in the β-stiffness index tended to correlate negatively with the corresponding changes in MAP (r=−0.31, P=0.07). These results suggest that carotid artery compliance remains unchanged during the systemic NOS inhibition in spite of systemic vasoconstriction.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Nichols W, O'Rourke MF . McDonald's Blood Flow in Arteries 5th Ed. Theoretical, Experimental and Clinical Principles. Arnold: London, 2005.

    Google Scholar 

  2. 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 (1): 50–58.

    Article  CAS  Google Scholar 

  3. McEniery CM, Yasmin Hall IR, Qasem A, Wilkinson IB, Cockcroft JR . Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: the Anglo-Cardiff Collaborative Trial (ACCT). J Am Coll Cardiol 2005; 46 (9): 1753–1760.

    Article  Google Scholar 

  4. 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 (5): 1111–1117.

    Article  CAS  Google Scholar 

  5. Lakatta EG . Age-associated cardiovascular changes in health: impact on cardiovascular disease in older persons. Heart Fail Rev 2002; 7 (1): 29–49.

    Article  Google Scholar 

  6. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001; 37 (5): 1236–1241.

    Article  CAS  Google Scholar 

  7. Agabiti-Rosei E, Muiesan ML . Carotid atherosclerosis, arterial stiffness and stroke events. Adv Cardiol 2007; 44: 173–186.

    Article  CAS  Google Scholar 

  8. Baumbach GL, Siems JE, Heistad DD . Effects of local reduction in pressure on distensibility and composition of cerebral arterioles. Circ Res 1991; 68 (2): 338–351.

    Article  CAS  Google Scholar 

  9. Mitchell GF . Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage. J Appl Physiol 2008; 105 (5): 1652–1660.

    Article  Google Scholar 

  10. Tanaka H, Safar ME . Influence of lifestyle modification on arterial stiffness and wave reflections. Am J Hypertens 2005; 18 (1): 137–144.

    Article  Google Scholar 

  11. 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.

    Article  CAS  Google Scholar 

  12. Fitch RM, Vergona R, Sullivan ME, Wang YX . Nitric oxide synthase inhibition increases aortic stiffness measured by pulse wave velocity in rats. Cardiovasc Res 2001; 51 (2): 351–358.

    Article  CAS  Google Scholar 

  13. Stewart AD, Millasseau SC, Kearney MT, Ritter JM, Chowienczyk PJ . Effects of inhibition of basal nitric oxide synthesis on carotid-femoral pulse wave velocity and augmentation index in humans. Hypertension 2003; 42 (5): 915–918.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. Wesseling KH, Jansen JR, Settels JJ, Schreuder JJ . Computation of aortic flow from pressure in humans using a nonlinear, three-element model. J Appl Physiol 1993; 74 (5): 2566–2573.

    Article  CAS  Google Scholar 

  16. Gratz I, Kraidin J, Jacobi AG, deCastro NG, Spagna P, Larijani GE . Continuous noninvasive cardiac output as estimated from the pulse contour curve. J Clin Monit 1992; 8 (1): 20–27.

    Article  CAS  Google Scholar 

  17. Jansen JR, Wesseling KH, Settels JJ, Schreuder JJ . Continuous cardiac output monitoring by pulse contour during cardiac surgery. Eur Heart J 1990; 11 (Suppl I): 26–32.

    Article  Google Scholar 

  18. Stok WJ, Baisch F, Hillebrecht A, Schulz H, Meyer M, Karemaker JM . Noninvasive cardiac output measurement by arterial pulse analysis compared with inert gas rebreathing. J Appl Physiol 1993; 74 (6): 2687–2693.

    Article  CAS  Google Scholar 

  19. Sugawara J, Tanabe T, Miyachi M, Yamamoto K, Takahashi K, Iemitsu M et al. Non-invasive assessment of cardiac output during exercise in healthy young humans: comparison between Modelflow method and Doppler echocardiography method. Acta Physiol Scand 2003; 179 (4): 361–366.

    Article  CAS  Google Scholar 

  20. Sugawara J, Komine H, Hayashi K, Yoshizawa M, Otsuki T, Shimojo N et al. Reduction in alpha-adrenergic receptor-mediated vascular tone contributes to improved arterial compliance with endurance training. Int J Cardiol 2009; 135 (3): 346–352.

    Article  Google Scholar 

  21. Tanaka H, Dinenno FA, Monahan KD, Clevenger CM, DeSouza CA, Seals DR . Aging, habitual exercise, and dynamic arterial compliance. Circulation 2000; 102: 1270–1275.

    Article  CAS  Google Scholar 

  22. Armentano R, Megnien JL, Simon A, Bellenfant F, Barra J, Levenson J . Effects of hypertension on viscoelasticity of carotid and femoral arteries in humans. Hypertension 1995; 26 (1): 48–54.

    Article  CAS  Google Scholar 

  23. Hirai T, Sasayama S, Kawasaki T, Yagi S . Stiffness of systemic arteries in patients with myocardial infarction. A noninvasive method to predict severity of coronary atherosclerosis. Circulation 1989; 80 (1): 78–86.

    Article  CAS  Google Scholar 

  24. Reneman RS, van Merode T, Hick P, Muytjens AM, Hoeks AP . Age-related changes in carotid artery wall properties in men. Ultrasound Med Biol 1986; 12 (6): 465–471.

    Article  CAS  Google Scholar 

  25. Roman MJ, Pini R, Pickering TG, Devereux RB . Non-invasive measurements of arterial compliance in hypertensive compared with normotensive adults. J Hypertens Suppl 1992; 10 (6): S115–S118.

    CAS  PubMed  Google Scholar 

  26. Sugawara J, Hayashi K, Tanaka H . Distal shift of arterial pressure wave reflection sites with aging. Hypertension 2010; 56 (5): 920–925.

    Article  CAS  Google Scholar 

  27. Mitchell GF, Parise H, Benjamin EJ, Larson MG, Keyes MJ, Vita JA et al. Changes in arterial stiffness and wave reflection with advancing age in healthy men and women: the Framingham Heart Study. Hypertension 2004; 43 (6): 1239–1245.

    Article  CAS  Google Scholar 

  28. Murgo JP, Westerhof N, Giolma JP, Altobelli SA . Aortic input impedance in normal man: relationship to pressure wave forms. Circulation 1980; 62 (1): 105–116.

    Article  CAS  Google Scholar 

  29. 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 (2): 189–192.

    Article  CAS  Google Scholar 

  30. Sugawara J, Komine H, Hayashi K, Yoshizawa M, Yokoi T, Otsuki T et al. Effect of systemic nitric oxide synthase inhibition on arterial stiffness in humans. Hypertens Res 2007; 30 (5): 411–415.

    Article  CAS  Google Scholar 

  31. Frewin DB, Whelan RF . The mechanism of action of tyramine on the blood vessels of the forearm in man. Br J Pharmacol Chemother 1968; 33 (1): 105–116.

    Article  CAS  Google Scholar 

  32. Saeed M, Sommer O, Holtz J, Bassenge E . Alpha-adrenoceptor blockade by phentolamine causes beta-adrenergic vasodilation by increased catecholamine release due to presynaptic alpha-blockade. J Cardiovasc Pharmacol 1982; 4 (1): 44–52.

    Article  CAS  Google Scholar 

  33. Kang KB, van der Zypp A, Majewski H . Endogenous nitric oxide attenuates beta-adrenoceptor-mediated relaxation in rat aorta. Clin Exp Pharmacol Physiol 2007; 34 (1-2): 95–101.

    Article  CAS  Google Scholar 

  34. Sanbe A, Tanaka Y, Fujiwara Y, Miyauchi N, Mizutani R, Yamauchi J et al. Enhanced vascular contractility in alpha1-adrenergic receptor-deficient mice. Life Sci 2009; 84 (21-22): 713–718.

    Article  CAS  Google Scholar 

  35. Avolio AP, Van Bortel LM, Boutouyrie P, Cockcroft JR, McEniery CM, Protogerou AD et al. Role of pulse pressure amplification in arterial hypertension: experts' opinion and review of the data. Hypertension 2009; 54 (2): 375–383.

    Article  CAS  Google Scholar 

  36. Safar ME, Protogerou AD, Blacher J . Statins central blood pressure, and blood pressure amplification. Circulation 2009; 119 (1): 9–12.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (18300215 and 18650186), JSPS Postdoctoral Fellowships for Research Abroad and NIH grant AG20966.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J Sugawara.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sugawara, J., Saito, Y., Maeda, S. et al. Lack of changes in carotid artery compliance with systemic nitric oxide synthase inhibition. J Hum Hypertens 28, 494–499 (2014). https://doi.org/10.1038/jhh.2013.137

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2013.137

Keywords

This article is cited by

Search

Quick links