Format

Send to

Choose Destination
EBioMedicine. 2018 Nov;37:259-268. doi: 10.1016/j.ebiom.2018.10.039. Epub 2018 Nov 8.

Dissociation between urate and blood pressure in mice and in people with early Parkinson's disease.

Author information

1
Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. Electronic address: xchen17@mgh.harvard.edu.
2
Department of Neurology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
3
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Gray-Bigelow 444, 55 Fruit Street, Boston, MA 02114, USA.
4
Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
5
Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
6
Statistics Center, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.

Abstract

BACKGROUND:

Epidemiological, laboratory and clinical studies have established an association between elevated urate and high blood pressure (BP). However, the inference of causality remains controversial. A naturally occurring antioxidant, urate may also be neuroprotective, and urate-elevating treatment with its precursor inosine is currently under clinical development as a potential disease-modifying strategy for Parkinson's disease (PD).

METHODS:

Our study takes advantage of a recently completed phase II trial evaluating oral inosine in de novo non-disabling early PD with no major cardiovascular and nephrological conditions, and of three lines of genetically engineered mice: urate oxidase (UOx) global knockout (gKO), conditional KO (cKO), and transgenic (Tg) mice with markedly elevated, mildly elevated, and substantially reduced serum urate, respectively, to systematically investigate effects of urate-modifying manipulation on BP.

FINDINGS:

Among clinical trial participants, change in serum urate but not changes in systolic, diastolic and orthostatic BP differed by treatment group. There was no positive correlation between urate elevations and changes in systolic, diastolic and orthostatic BP ((p = .05 (in inverse direction), 0.30 and 0.63, respectively)). Between UOx gKO, cKO, or Tg mice and their respective wildtype littermates there were no significant differences in systolic or diastolic BP or in their responses to BP-regulating interventions.

INTERPRETATION:

Our complementary preclinical and human studies of urate modulation in animal models and in generally healthy early PD do not support a hypertensive effect of urate elevation or an association between urate and BP. FUND: U.S. Department of Defense, RJG Foundation, Michael J. Fox Foundation LEAPS program, National Institutes of Health, American Federation for Aging Research, Parkinson's Disease Foundation Advancing Parkinson's Therapies initiative.

KEYWORDS:

Blood pressure; Hypertension; Hyperuricemia; Urate; Urate oxidase

PMID:
30415890
PMCID:
PMC6284456
DOI:
10.1016/j.ebiom.2018.10.039
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center