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Effect of Tetrahydrobiopterin on Blood Pressure in Rats after Subtotal Nephrectomy
- Source :
- Nephron Physiology. 94:p6-p9
- Publication Year :
- 2003
- Publisher :
- S. Karger AG, 2003.
-
Abstract
- Background: Previous studies have shown that endothelial dysfunction after 5/6 nephrectomy (5/6 Nx) in rats is associated with decreased nitric oxide (NO) bioavailability and increased vascular superoxide production. Blood pressure is significantly increased by day 10 after surgery. Tetrahydrobiopterin (BH4) is a key cofactor of NO synthase. Suboptimal levels of BH4 result in uncoupling of NO synthase, low NO synthesis and augmented production of superoxide anions. The aim of this study was to evaluate whether BH4 supplementation may improve NO production and prevent the increase of blood pressure after 5/6 Nx. Methods: Three groups were evaluated: 5/6 Nx (untreated rats), BH4 (5/6 Nx rats treated with BH4, 10 mg/day i.p. for 10 days) and L-ARG (5/6 Nx rats treated with L-arginine, 260 mg/kg BW, p.o for 10 days). Systolic blood pressure (SBP), urinary nitrate excretion (UNO3) and creatinine clearance (CCR) were measured before surgery and on days 3 and 10 after surgery. Endothelial NO synthase (eNOS) protein content of mesenteric resistance vessels was measured at the end of the study. Results: SBP increased from 107 ± 2 to 127 ± 4 mm Hg in untreated 5/6 Nx rats (p < 0.01). By contrast, rats treated with BH4 or L-ARG remained normotensive. Ten days after 5/6 Nx, creatinine clearance decreased similarly in all groups. Both BH4 and L-ARG supplementation markedly increased UNO3 excretion. The mesenteric vascular expression of eNOs protein was significantly higher in BH4 but not in L-ARG, compared with Nx rats. Conclusions: BH4 supplementation prevents the earlier increase in blood pressure observed in rats after 5/6 Nx, possibly by upregulating eNOS in resistance vessels.
- Subjects :
- Male
medicine.medical_specialty
Nitric Oxide Synthase Type III
Physiology
medicine.medical_treatment
Hemodynamics
Blood Pressure
Arginine
Kidney
Nitric Oxide
Nephrectomy
Nitric oxide
chemistry.chemical_compound
Physiology (medical)
Internal medicine
medicine
Animals
Renal Insufficiency
Kidney surgery
Rats, Wistar
Endothelial dysfunction
Nitrates
Chemistry
General Medicine
Tetrahydrobiopterin
medicine.disease
Biopterin
Mesenteric Arteries
Rats
Endocrinology
Blood pressure
Nephrology
Creatinine
Hypertension
Nitric Oxide Synthase
medicine.drug
Subjects
Details
- ISSN :
- 16602137
- Volume :
- 94
- Database :
- OpenAIRE
- Journal :
- Nephron Physiology
- Accession number :
- edsair.doi.dedup.....c79e327ed784a1f0665499f62a01e17b