Endothelial function and oxidative stress in renovascular hypertension.

BACKGROUND It has been reported that renovascular hypertension activates the renin-angiotensin system, leading to an increase in oxidative stress. We sought to determine whether renal-artery angioplasty improves endothelial dysfunction in patients with renovascular hypertension through a reduction in oxidative stress. METHODS We evaluated the response of forearm blood flow to acetylcholine, an endothelium-dependent vasodilator, and isosorbide dinitrate, an endothelium-independent vasodilator, before and after renal-artery angioplasty in 15 subjects with renovascular hypertension and 15 controls without hypertension who were matched for age and sex. Forearm blood flow was measured with the use of a mercury-filled Silastic strain-gauge plethysmograph. RESULTS The forearm blood flow in response to acetylcholine was less in subjects with renovascular hypertension than in controls, although the forearm blood flow in response to isosorbide dinitrate was similar in the two groups. Angioplasty decreased systolic and diastolic blood pressures, forearm vascular resistance, and urinary excretion of 8-hydroxy-2'-deoxyguanosine and serum malondialdehyde-modified low-density lipoprotein (LDL), indexes of oxidative stress. After angioplasty, the mean (+/-SD) forearm blood flow in response to acetylcholine was increased in the patients with renovascular hypertension (19.3+/-6.8 vs. 29.6+/-7.1 ml per minute per 100 ml, P=0.002). The increase in the maximal forearm blood flow in response to acetylcholine correlated significantly with the decrease in urinary excretion of 8-hydroxy-2'-deoxyguanosine (r=-0.51, P=0.004) and serum malondialdehyde-modified LDL (r=-0.39, P=0.02). Coinfusion of ascorbic acid (vitamin C) augmented the response of forearm blood flow to acetylcholine before angioplasty (P<0.001) but not after angioplasty. CONCLUSIONS These findings suggest that excessive oxidative stress is involved, at least in part, in impaired endothelium-dependent vasodilatation in patients with renovascular hypertension.

[1]  G. Kajiyama,et al.  Effect of the angiotensin-converting enzyme inhibitor imidapril on reactive hyperemia in patients with essential hypertension: relationship between treatment periods and resistance artery endothelial function. , 2001, Journal of the American College of Cardiology.

[2]  C. Napoli,et al.  Increased Oxidative Stress in Experimental Renovascular Hypertension , 2001, Hypertension.

[3]  D. Harrison,et al.  Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. , 2000, Circulation research.

[4]  G. Kajiyama,et al.  A comparison of angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers and diuretic agents on reactive hyperemia in patients with essential hypertension: a multicenter study. , 2000, Journal of the American College of Cardiology.

[5]  J. C. Romero,et al.  State-of-the-Art lecture. Role of angiotensin and oxidative stress in essential hypertension. , 1999, Hypertension.

[6]  G. Kajiyama,et al.  Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects: role of endothelium-derived nitric oxide. , 1999, Circulation.

[7]  T. Rabelink,et al.  Acute simultaneous stimulation of nitric oxide and oxygen radicals by angiotensin II in humans in vivo. , 1999, Journal of cardiovascular pharmacology.

[8]  H. Drexler,et al.  Endothelial dysfunction in human disease. , 1999, Journal of molecular and cellular cardiology.

[9]  M. Dikshit,et al.  Alterations in the vasoreactivity of hypertensive rat aortic rings: role of nitric oxide and superoxide radicals. , 1998, Clinical and experimental hypertension.

[10]  L. Ghiadoni,et al.  Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. , 1998, Circulation.

[11]  E. Porteri,et al.  Endothelial dysfunction in hypertension is independent from the etiology and from vascular structure. , 1998, Hypertension.

[12]  T. Lehtimäki,et al.  New biomarker evidence of oxidative DNA damage in patients with non‐insulin‐dependent diabetes mellitus , 1997, FEBS letters.

[13]  Y. Konishi,et al.  Involvement of 8-hydroxyguanine formation in the initiation of rat liver carcinogenesis by low dose levels of N-nitrosodiethylamine. , 1997, Cancer research.

[14]  T. Ogihara,et al.  Converting enzyme inhibitor improves forearm reactive hyperemia in essential hypertension. , 1997, Hypertension.

[15]  D. Harrison,et al.  Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. , 1996, The Journal of clinical investigation.

[16]  E. Schiffrin,et al.  Comparison of effects of angiotensin I-converting enzyme inhibition and beta-blockade for 2 years on function of small arteries from hypertensive patients. , 1995, Hypertension.

[17]  E. Miller,et al.  Immunization of low density lipoprotein (LDL) receptor-deficient rabbits with homologous malondialdehyde-modified LDL reduces atherogenesis. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[18]  G. Bellomo,et al.  Presence of autoantibodies against oxidatively modified low‐density lipoprotein in essential hypertension: a biochemical signature of an enhanced in vivo low‐density lipoprotein oxidation , 1995, Journal of hypertension.

[19]  M. Creager,et al.  Effect of captopril and enalapril on endothelial function in hypertensive patients. , 1994, Hypertension.

[20]  A. Salvetti,et al.  Vasodilation to acetylcholine in primary and secondary forms of human hypertension. , 1993, Hypertension.

[21]  A. Quyyumi,et al.  Role of Endothelium‐Derived Nitric Oxide in the Abnormal Endothelium‐Dependent Vascular Relaxation of Patients With Essential Hypertension , 1993, Circulation.

[22]  J. Faber,et al.  Interaction between microvascular alpha 1- and alpha 2-adrenoceptors and endothelium-derived relaxing factor. , 1992, Circulation research.

[23]  J. Salonen,et al.  Autoantibody against oxidised LDL and progression of carotid atherosclerosis , 1992, The Lancet.

[24]  M. Daemen,et al.  Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall. , 1991, Circulation research.

[25]  T. Lüscher,et al.  Activation of endothelial L-arginine pathway in resistance arteries. Effect of age and hypertension. , 1990, Hypertension.

[26]  A. Quyyumi,et al.  Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. , 1990, The New England journal of medicine.

[27]  B. Ames,et al.  Oxidative damage to DNA during aging: 8-hydroxy-2'-deoxyguanosine in rat organ DNA and urine. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[28]  T. Tanaka,et al.  Release of norepinephrine from adrenergic nerve endings of blood vessels is modulated by endothelium-derived relaxing factor. , 1990, American journal of hypertension.