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Nitric oxide and hypercholesterolemia: a matter of oxidation and reduction?

1998; Elsevier BV; Volume: 137; Linguagem: Inglês

10.1016/s0021-9150(97)00304-3

1879-1484

Robert Wever, Erik S.G. Stroes, Ton J. Rabelink,

Renin-Angiotensin System Studies

In the last two decades the endothelium has emerged as a vital organ that regulates both vascular tone and structure [ 1 Moncada S Higgs A. The l-arginine-nitric oxide pathway. New Engl J Med. 1993; 329: 2002-2011 Crossref PubMed Scopus (4201) Google Scholar , 2 Gimbrone MA. Vascular endothelium: an integrator of pathophysiologic stimuli in atherosclerosis. Am J Cardiol. 1995; 75: 67b-70 Abstract Full Text PDF PubMed Scopus (132) Google Scholar , 3 Busse R Fleming I. Regulation and functional consequences of endothelial nitric oxide formation. Ann Med. 1995; 27: 331-340 Crossref PubMed Google Scholar ]. The endothelium at the same time produces vasoconstrictor and vasodilator, as well as proliferative and anti-proliferative factors [ 1 Moncada S Higgs A. The l-arginine-nitric oxide pathway. New Engl J Med. 1993; 329: 2002-2011 Crossref PubMed Scopus (4201) Google Scholar , 2 Gimbrone MA. Vascular endothelium: an integrator of pathophysiologic stimuli in atherosclerosis. Am J Cardiol. 1995; 75: 67b-70 Abstract Full Text PDF PubMed Scopus (132) Google Scholar , 3 Busse R Fleming I. Regulation and functional consequences of endothelial nitric oxide formation. Ann Med. 1995; 27: 331-340 Crossref PubMed Google Scholar ]. Evidence is accumulating that nitric oxide (NO)-activity is an important determinant in normal vessel wall homeostasis [ 4 Palmer RMJ Ferrige AG Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987; 327: 534-536 Crossref Google Scholar , 5 Anggard E. Nitric oxide: mediator, murderer and medicine. Lancet. 1994; 343: 1199-1206 Abstract PubMed Scopus (611) Google Scholar ]. In vitro, NO inhibits all key processes involved in the early pathogenesis of vascular injury and atherosclerosis (Table 1). It is, therefore, of importance that major risk factors for atherosclerosis, such as smoking [ 6 Heitzer T Yla-Herttuala S Luoma J Kurz S Munzel T Just H Olschewski M Drexler H. Cigarette smoking potentiates endothelial dysfunction of forearm resistance vessels in patients with hypercholesterolemia. Role of oxidized LDL. Circulation. 1996; 93: 1346-1353 Crossref PubMed Google Scholar , 7 Celermajer DS Sorensen KE Georgakopoulos D Bull C Thomas O Robinson J Deanfield JE. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation. 1993; 88: 2149-2155 Crossref PubMed Google Scholar , 8 Heitzer T Just H Munzel T. Antioxidant vitamin C improves endothelial dysfunction in chronic smokers. Circulation. 1996; 94: 6-9 Crossref PubMed Google Scholar , 9 Celermajer DS Adams MR Clarkson P Robinson J McCredie R Donald A Deanfield JE. Passive smoking and impaired endothelium-dependent arterial dilatation in healthy young adults. 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Impairment of endothelium-dependent dilation is an early event in children with familial hypercholesterolemia and is related to the lipoprotein(a) level. J Clin Invest. 1994; 93: 50-55 Crossref PubMed Google Scholar , 33 Kari JA Donald AE Vallance DT Bruckdorfer KR Leone A Mullen MJ Bunce T Dorado B Deanfield JE Rees L. Physiology and biochemistry of endothelial function in children with chronic renal failure. Kidney Int. 1997; 52: 468-472 Crossref PubMed Google Scholar ], preceding the advent of structural alterations [ 34 Reddy KG Nair RN Sheehan HM Hodgson JM. Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis. J Am Coll Cardiol. 1994; 23: 833-843 Abstract Full Text PDF PubMed Google Scholar ]. As a consequence, NO-activity has been put forward as pseudo-endpoint for cardiovascular morbidity and mortality, potentially allowing early identification of cardiovascular risk as well as monitoring of clinical benefit of instituted therapy aimed at reducing cardiovascular risk [ 35 Luscher TF. The endothelium as target and mediator of cardiovascular disease. Eur J Clin Invest. 1993; 23: 670-685 Crossref PubMed Google Scholar ]. In the present review we will focus on NO-activity during hypercholesterolemia. Indeed, NO-activity is impaired in hypercholesterolemic patients [ 11 Creager M Cooke JP Mendelsohn ME. Impaired vasodilatation of forearm resistance vessels in hypercholesterolemic humans. J Clin Invest. 1990; 86: 228-234 Crossref PubMed Google Scholar , 12 Chowienczyk PJ Watts GF Cockroft JR Ritter JM. Impaired endothelium-dependent vasodilation of forearm resistance vessels in hypercholesterolemia. 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