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Nitric oxide in systemic and pulmonary hypertension

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Journal of Biomedical Science

Abstract

Endothelium-derived nitric oxide (NO) is an important gas molecule in the regulation of vascular tone and arterial pressure. It has been considered that endothelial dysfunction with impairment of NO production contributes to a hypertensive state. Alternatively, long-term hypertension may affect the endothelial function, depress NO production, and thereby reduce the dilator action on vasculatures. There were many studies to support that endothelium-dependent vasodilatation was impaired in animals and humans with long-term hypertension. However, results of some reports were not always consistent with this consensus. Recent experiments in our laboratory revealed that an NO synthase inhibitor, NG-nitro-L-arginine monomethyl ester (L-NAME) caused elevation of arterial pressure (AP) in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). The magnitude of AP increase following NO blockade with L-NAME was much higher in SHR than WKY. In other experiments with the use of arterial impedance analysis, we found that L-NAME slightly or little affected the pulsatile hemodynamics including characteristic impedance, wave reflection and ventricular work. Furthermore, these changes were not different between SHR and WKY. The increase in AP and total peripheral resistance (TPR) following NO blockade in SHR were significantly greater than those in WKY, despite higher resting values of AP and TPR in SHR. In connection with the results of other studies, we propose that heterogeneity with respect to the involvement of NO (impairment, no change or enhancement) in the development of hypertension may exist among animal species, hypertensive models and different organ vessels. Our study in SHR provide evidence to indicate that the effects of basal release of NO on the arterial pressure and peripheral resistance are not impaired, but enhanced in the hypertensive state. The increase in NO production may provide a compensatory mechanism to keep the blood pressure and peripheral resistance at lower levels. The phenomenon of enhanced NO release also occurs in certain type of pulmonary hypertension. We first hypothesized that a decrease in NO formation might be responsible for the pulmonary vasoconstriction during hypoxia. With the measurement of NO release in the pulmonary vein, we found that ventilatory hypoxia produced pulmonary hypertension accompanying an increase in NO production. Addition of NO inhibitor (L-NAME), blood or RBC into the perfusate attenuated or abolished the NO release, while potentiating pulmonary vasoconstriction. During hypoxia, the increased NO formation in the pulmonary circulation similarly exerts a compensatory mechanism to offset the degree of pulmonary vasoconstriction.

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References

  1. Amezcua JL, Palmer RMJ, Souza BM, Moncada S. Nitric oxide synthesized from L-arginine regulates vascular tone in the coronary circulation of the rabbit. Br J Pharmacol 97:1119–1124;1989.

    PubMed  Google Scholar 

  2. Archer SL. Comparison of the hemodynamic effects of nitric oxide and endothelium-dependent vasodilators in intact lungs. J Appl Physiol 68:735–747;1990.

    PubMed  Google Scholar 

  3. Arnal JF, Amrani AIE, Chatellier G, Menard J, Michel JB. Cardiac weight in hypertension induced by nitric oxide synthase blockade. Hypertension 22:380–387;1993.

    Google Scholar 

  4. Bredt DS, Snyder SH. Nitric oxide: A physiologic messenger molecule. Ann Rev Biochem 63:175–195;1994.

    Article  PubMed  Google Scholar 

  5. Chang KC, Hsieh KS, Kuo TS, Chen HI. Effects of nifedipine on systemic hydraulic vascular load in patients with hypertension. Cardiovasc Res 24:719–726;1990.

    PubMed  Google Scholar 

  6. Chen HI. Nitric oxide in arterial hemodynamics: A comparison between normotension and hypertension. 12th Joint Conf Biomed Sci Symposium II: Cardiovascular Homeostasis, 112(S5);1997.

  7. Chen HI, Hu CT. Assessment of arterial hemodynamics with aortic impedance analysis: Effects of acute nitric oxide blockade in the rat. Proc 2nd Congress of CV Medicine in Chinese Society (U. of Beijing), 3–9;1997.

  8. Chen HI, Hu CT, Chang KC. Characterization of arterial hemodynamics in rats with established hypertension. Chinese J Physiol 39:49–55;1996.

    Google Scholar 

  9. Fozard JR, Part ML. Haemodynamic responses to NG-monomethyl-L-arginine in spontaneously hypertensive and normotensive Wistar-Kyoto rats. Br J Pharmacol 102:823–826;1991.

    PubMed  Google Scholar 

  10. Fratacci MD, Frostell CG, Chen TY, Wain JC, Robinson DR, Zapol WM. Inhaled nitric oxide: A selective pulmonary vasodilator of heparin-protamine vasoconstriction in sheep. Anesthesiology 75:990–999;1991.

    PubMed  Google Scholar 

  11. Frostell CG, Fratacci MD, Wain JC, Jones R, Zapol WM. Inhaled nitric oxide: A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction. Circulation 83:2038–2047;1991.

    PubMed  Google Scholar 

  12. Gardiner SM, Compton AM, Bennett T, Palmer RMJ, Moncada S. Control of regional blood flow by endothelium-derived nitric oxide. Hypertension 15:486–492;1990.

    PubMed  Google Scholar 

  13. Gardiner SM, Compton AM, Kemp PA, Bennett T. Regional and cardiac haemodynamic effects of NG-nitricL-arginine methyl ester in conscious Long-Evans rats. Br J Pharmacol 101:625–631;1990.

    PubMed  Google Scholar 

  14. Giuliani P, Dona GC, Andriuoli G, Del Soldato P. NG-monomethyl-L-arginine inhibits endothelium-dependent relaxation induced by N-α-benzoyl-L-arginine in rat aorta. In: Moncada S, Higgs EA, eds. Nitric Oxide fromL-Arginine: A Bioregulatory System. Amsterdam, Elsevier, 393–395;1990.

    Google Scholar 

  15. Griffith TM, Edwards DH, Davies RL, Harrison TJ, Evans KT. EDRF coordinates the behavior of vascular resistance vessels. Nature 329:442–445;1987.

    Article  PubMed  Google Scholar 

  16. Hu CT, Chang KC, Kuo TS, Chen HI. The correlation of cardiac mass with arterial haemodynamics of resistive and capacitive load in rats with normotension and established hypertension. Pflügers Arch 428:533–541;1994.

    Article  Google Scholar 

  17. Ignarro LJ, Byrns RE, Buga GM, Wood KS. Endothelium-derived relaxing factor from pulmonary artery and vein possesses pharmacologic and chemical properties identical to those of nitric oxide radical. Circ Res 61:866–879;1987.

    PubMed  Google Scholar 

  18. Katusic ZS, Moncada S, Vanhoutte PM. Inhibitor effect of NG-monomethyl-L-arginine on endothelium-dependent relaxations to vasopressin. In: Moncada S, Higgs EA, eds. Nitric Oxide fromL-Arginine: A Bioregulatory System. Amsterdam, Elsevier, 69–72;1990.

    Google Scholar 

  19. Lacolley PJ, Lewis SJ, Brody MJ.L-NG-nitroarginine produces an exaggerated hypertension in anesthetized SHR. Eur J Pharmacol 197:239–240;1991.

    Article  PubMed  Google Scholar 

  20. Lee L, Webb RC. Endothelium-dependent relaxation andL-arginine metabolism in genetic hypertension. Hypertension 19:435–441;1992.

    PubMed  Google Scholar 

  21. Levi R, Gross S, Lamparter B, Fasehyn OA, Aisaka K, Jaffe EA, Griffith OW, Stueher DJ. Evidence thatL-arginine is the biosynthetic precursor of vascular and cardiac nitric oxide. In: Moncada S, Higgs EA, eds. Nitric Oxide fromL-Arginine: A Bioregulatory System. Amsterdam, Elsevier, 35–45;1990.

    Google Scholar 

  22. Li J, Bukoski RD. Endothelium-dependent relaxation of hypertensive resistance arteries is not impaired under all conditions. Circ Res 72:290–296;1993.

    PubMed  Google Scholar 

  23. Linder L, Kiowski W, Buhler FR, Lüscher TF. Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo: Blunted response in essential hypertension. Circulation 81:1762–1767;1990.

    PubMed  Google Scholar 

  24. Lockette W, Otsuka Y, Carretero O. The loss of endothelium-dependent relaxation in hypertension. Hypertension 8 (suppl II):II61-II66;1986.

    PubMed  Google Scholar 

  25. Lüscher TF. The endothelium in hypertension: Bystander, target or mediator? J Hypertens 12 (suppl 10):S105-S116;1994.

    Google Scholar 

  26. Lüscher TF, Raij L, Vanhoutte PM. Endothelium-dependent responses in normotensive and hypertensive Dahl rats. Hypertension 9:157–163;1987.

    PubMed  Google Scholar 

  27. Lüscher TF, Vanhoutte PM. Hypertension and endothelium-dependent response. In: Vanhoutte PM, ed. Vasodilation. New York, Raven Press, 523–529;1988.

    Google Scholar 

  28. Manning RD, Hu L, Mizelle HL, Nafz B, Wittmann U, Kirchheim HR. Cardiovascular response to long-term blockade of nitric oxide synthesis. Hypertension 20:40–48;1993.

    Google Scholar 

  29. Mayhan WG, Faraci FM, Heistad DD. Impairment of endothelium-dependent responses of cerebral arterioles in chronic hypertension. Am J Physiol 253:H1435-H1440;1987.

    PubMed  Google Scholar 

  30. Mayhan WG, Faraci FM, Heistad DD. Responses of cerebral arterioles to adenosine diphosphate, serotonin and the thromboxane analogue U-46619 during chronic hypertension. Hypertension 12 (suppl VI):V1556-V1561;1989.

    Google Scholar 

  31. Milnor WR. Hemodynamics, ed 2. Baltimore, Williams & Wilkins, 11–41;1989.

    Google Scholar 

  32. Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: Physiology, pathophysiology and pharmacology. Pharmacol Rev 43:109–142;1991.

    PubMed  Google Scholar 

  33. Moncada S, Radomski MW, Palmer RMJ. Endothelium-derived relaxing factor: Identification as nitric oxide and role in the control of vascular tone and platelet function. Biochem Pharmacol 37:2495–2501;1988.

    Article  PubMed  Google Scholar 

  34. Mourlon-Le-Grand MC, Benessiano J, Levy BI. cGMP pathway and mechanical properties of carotid artery wall in WKY rats and SHR: Role of Endothelium. Am J Physiol 263:H61-H67;1992.

    PubMed  Google Scholar 

  35. O'Rourke MF. Vascular impedance: the relationship between pressure and flow. In: O'Rourke MF, ed. Arterial Function in Health and Disease. London, Livingstone/Churchill, 94–132;1982.

    Google Scholar 

  36. Palmer RMJ, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526;1987.

    PubMed  Google Scholar 

  37. Palmer RMJ, Rees DD, Ashton DS, Moncada S.L-Arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun 153:1251–1256;1988.

    Article  PubMed  Google Scholar 

  38. Panza JA, Quyyumi AA, Brush JE Jr, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 323:22–27;1990.

    PubMed  Google Scholar 

  39. Pepke-Zaba J, Higenbottan TW, Dinh-Xuan AT, Stone D, Wallwork J. Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet 338:1173–1174;1991.

    Article  PubMed  Google Scholar 

  40. Rees DD, Palmer RMJ, Moncada S. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci USA 86:3375–3378;1989.

    PubMed  Google Scholar 

  41. Rees DD, Palmer RMJ, Schulz R, Hodson HF, Moncada S. Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol 101:746–752;1990.

    PubMed  Google Scholar 

  42. Sakuma I, Stuehr DJ, Gross SS, Nathan C, Levi R. Identification of arginine as a precursor of endothelium-derived relaxing factor. Proc Natl Acad Sci USA 85:8664–8667;1988.

    PubMed  Google Scholar 

  43. Taddei S, Virdis A, Mattei P, Salvetti A. Vasodilation to acetylcholine in primary and secondary forms of human hypertension. Hypertension 21:929–933;1993.

    PubMed  Google Scholar 

  44. Thomas G, Cole EA, Ramwell PW. NG-monomethylL-arginine is a nonspecific inhibitor of vascular relaxation. Eur J Pharmacol 170:123–124;1989.

    Article  PubMed  Google Scholar 

  45. Wang D, Hsu K, Hwang CP, Chen HI. Measurement of nitric oxide release in the isolated perfused rat lung. Biochem Biophys Res Commun 208:1016–1020;1993.

    Article  Google Scholar 

  46. Ward JE, Angus JA. Acute and chronic inhibition of nitric oxide synthase in conscious rabbits: Role of nitric oxide in the control of vascular tone. J Cardiovasc Pharmacol 21:804–814;1993.

    PubMed  Google Scholar 

  47. Winquist RJ, Bunting PB, Baskin EP, Wallace AA. Decreased endothelium-dependent relaxation in New Zealand genetic hypertensive rats. J Hypertens 2:536–541;1984.

    Google Scholar 

  48. Wu CY, Yang ST, Chen HI. The pressor effects of constitutive and inducible nitric oxide synthase (NOS) inhibition: A comparison between hypertensive and normotensive rats of different ages. The 11th Joint Ann Conf Biomed Sci 116(A95);1996.

  49. Xiao J, Pang PKT. Does a general alteration in nitric oxide synthesis system occur in spontaneously hypertensive rats. Am J Physiol 266:H272-H278;1994.

    PubMed  Google Scholar 

  50. Yamazaki J, Fujita N, Nagao T. NG-monomethyl-L-arginine-induced pressor response at developmental and established stages in spontaneously hypertensive rats. J Pharmacol Exp Ther 259:52–57;1991.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Research, Cheng Hsin Medical Center, Taipei, Taiwan

    Hsing I. Chen MD, PhD, Cheng-Tao Hu, Chia-Yen Wu & David Wang

  2. Department of Physiology, Tzu Chi College of Medicine, 701, Section 3, Chung-Yan Rd., Hualien, Taiwan (ROC)

    Hsing I. Chen MD, PhD, Cheng-Tao Hu, Chia-Yen Wu & David Wang

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Chen, H.I., Hu, CT., Wu, CY. et al. Nitric oxide in systemic and pulmonary hypertension. J Biomed Sci 4, 244–248 (1997). https://doi.org/10.1007/BF02253424

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