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.
Higashi
Yukihito
Y
First Department of Internal Medicine, Hiroshima University, Faculty of Medicine, Hiroshima, Japan. yhigashi@hiroshima-u.ac.jp
Sasaki
Shota
S
Nakagawa
Keigo
K
Matsuura
Hideo
H
Oshima
Tetsuya
T
Chayama
Kazuaki
K
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000109:Acetylcholine / Q000008:administration & dosage; D000328:Adult; D017130:Angioplasty; D000804:Angiotensin II / Q000097:blood; D000975:Antioxidants / Q000008:administration & dosage; D001161:Arteriosclerosis / Q000150:complications; D001205:Ascorbic Acid / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001794:Blood Pressure; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular; D005260:Female; D005352:Fibromuscular Dysplasia / Q000150:complications; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006978:Hypertension, Renovascular / Q000150:complications / Q000503:physiopathology* / Q000628:therapy; D007548:Isosorbide Dinitrate / Q000008:administration & dosage; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D018384:Oxidative Stress; D012039:Regional Blood Flow; D012077:Renal Artery / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage
D000975:Antioxidants; D015415:Biomarkers; D008074:Lipoproteins; D014665:Vasodilator Agents; D000804:Angiotensin II; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D007548:Isosorbide Dinitrate; D000109:Acetylcholine; D001205:Ascorbic Acid