Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism.
Hyperuricemia is associated with hypertension and vascular disease, but whether this represents a causal relationship or an epiphenomenon remains unknown. We recently reported a model of mild hyperuricemia in rats that results in increased blood pressure and mild renal fibrosis. In this study, we examined the effect of hyperuricemia on the renal vasculature. Rats fed 2% oxonic acid and a low-salt diet for 7 wk developed mild hyperuricemia (1.8 vs. 1.4 mg/dl, P < 0.05), hypertension [147 vs. 127 mmHg systolic blood pressure (SBP), P < 0.05], and afferent arteriolar thickening, with a 35% increase in medial area (P < 0.05). Allopurinol or benziodarone prevented the hyperuricemia, hypertension, and arteriolopathy. Hydrochlorothiazide treatment did not prevent the hyperuricemia or arteriolopathy despite controlling blood pressure. In contrast, the arteriolopathy and hypertension were prevented by both enalapril and losartan. Uric acid also directly stimulated vascular smooth muscle cell proliferation in vitro, and this was partially inhibited by losartan. Thus hyperuricemia induces a renal arteriolopathy in rats that is blood pressure independent and involves the renin-angiotensin system.
Mazzali
Marilda
M
Division of Nephrology, Baylor College of Medicine, Houston, Texas 77030, USA.
Kanellis
John
J
Han
Lin
L
Feng
Lili
L
Xia
Yi-Yang
YY
Chen
Qiang
Q
Kang
Duk-Hee
DH
Gordon
Katherine L
KL
Watanabe
Susumu
S
Nakagawa
Takahiko
T
Lan
Hui Y
HY
Johnson
Richard J
RJ
D000284:Administration, Oral; D000493:Allopurinol / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology*; D001572:Benzofurans / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004232:Diuretics; D004656:Enalapril / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D010094:Oxonic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology; D017673:Sodium Chloride, Dietary; D014527:Uric Acid / Q000097:blood* / Q000494:pharmacology; D014528:Uricosuric Agents / Q000494:pharmacology; D014652:Vascular Diseases / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001572:Benzofurans; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D017673:Sodium Chloride, Dietary; D014528:Uricosuric Agents; D006852:Hydrochlorothiazide; D000804:Angiotensin II; D014527:Uric Acid; D010094:Oxonic Acid; D000493:Allopurinol; D004656:Enalapril; C058702:benziodarone; D019808:Losartan