Enalapril treatment restores the decreased proximal tubule reabsorption in response to acute volume expansion in diabetic rats

Tianzheng Yu, Ali A. Khraibi

Research output: Contribution to journalArticle

Abstract

The renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure, fluid and electrolyte homeostasis. The RAS is activated and renal interstitial hydrostatic pressure (RIHP) is decreased in diabetic rats. The objective of this study was to evaluate the roles of proximal tubule reabsorption and RAS in the decreased RIHP and blunted natriuretic and diuretic responses to acute saline volume expansion (VE) in diabetic rats. Enalapril was utilized to inhibit angiotensin II (AII) formation. Diabetes mellitus (DM) was induced by a single intraperitoneal (i.p.) injection of streptozotocin (STZ, 65 mg/kg). RIHP was measured by a polyethylene (PE) matrix that was chronically implanted in the left kidney. Fractional excretion of phosphate (FEPi) and fractional excretion of lithium (FELi) were used as indexes for proximal tubule reabsorption. VE significantly increased both FELi and FEPi in all groups of rats studied. However, the increase in FELi (ΔFELi = 17.26 ± 3.83%) and FEPi (ΔFEPi = 7.38 ± 2.37%) in diabetic rats (DC, n = 12) were significantly lower as compared with those in nondiabetic control rats (NC, n = 8; ΔFELi = 32.15 ± 4.71% and ΔFEPi = 20.62 ± 3.27%). The blunted increases in FELi and FEPi were associated with an attenuated increase in RIHP (ΔRIHP) in DC (1.8 ± 0.4 mm Hg) compared with NC rats (4.3 ± 0.3 mm Hg). Enalapril treatment (25 mg/kg/day in drinking water) had no effect on nondiabetic rats (NE, n = 8) as compared with untreated NC rats, but significantly improved RIHP response (ΔRIHP) to VE in diabetic rats (DE, n = 9; 2.8 ± 0.5 mm Hg). Both ΔFELi and ΔFEPi were restored by enalapril treatment in diabetic rats and no significant differences were found in ΔFELi and ΔFEPi between DE (ΔFELi = 26.81 ± 4.94% and ΔFEPi = 10.45 ± 4.67%) and NC groups of rats in response to VE. These data suggest that the activated RAS and the decrease in RIHP may play an important role in the increased proximal tubule reabsorption, and the attenuated natriuretic and diuretic responses to acute volume expansion in diabetic rats.

Original languageEnglish (US)
Pages (from-to)364-368
Number of pages5
JournalLife sciences
Volume83
Issue number9-10
DOIs
StatePublished - Aug 29 2008

Fingerprint

Enalapril
Rats
Lithium
Hydrostatic Pressure
Hydrostatic pressure
Kidney
Angiotensins
Renin
Renin-Angiotensin System
Therapeutics
Diuretics
Renal Reabsorption
Rat control
Blood pressure
Polyethylene
Streptozocin
Medical problems
Angiotensin II
Drinking Water
Intraperitoneal Injections

Keywords

  • Diabetes mellitus
  • Proximal tubule reabsorption
  • Renal interstitial hydrostatic pressure
  • Renin-angiotensin system
  • Volume expansion

ASJC Scopus subject areas

  • Pharmacology

Cite this

Enalapril treatment restores the decreased proximal tubule reabsorption in response to acute volume expansion in diabetic rats. / Yu, Tianzheng; Khraibi, Ali A.

In: Life sciences, Vol. 83, No. 9-10, 29.08.2008, p. 364-368.

Research output: Contribution to journalArticle

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abstract = "The renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure, fluid and electrolyte homeostasis. The RAS is activated and renal interstitial hydrostatic pressure (RIHP) is decreased in diabetic rats. The objective of this study was to evaluate the roles of proximal tubule reabsorption and RAS in the decreased RIHP and blunted natriuretic and diuretic responses to acute saline volume expansion (VE) in diabetic rats. Enalapril was utilized to inhibit angiotensin II (AII) formation. Diabetes mellitus (DM) was induced by a single intraperitoneal (i.p.) injection of streptozotocin (STZ, 65 mg/kg). RIHP was measured by a polyethylene (PE) matrix that was chronically implanted in the left kidney. Fractional excretion of phosphate (FEPi) and fractional excretion of lithium (FELi) were used as indexes for proximal tubule reabsorption. VE significantly increased both FELi and FEPi in all groups of rats studied. However, the increase in FELi (ΔFELi = 17.26 ± 3.83{\%}) and FEPi (ΔFEPi = 7.38 ± 2.37{\%}) in diabetic rats (DC, n = 12) were significantly lower as compared with those in nondiabetic control rats (NC, n = 8; ΔFELi = 32.15 ± 4.71{\%} and ΔFEPi = 20.62 ± 3.27{\%}). The blunted increases in FELi and FEPi were associated with an attenuated increase in RIHP (ΔRIHP) in DC (1.8 ± 0.4 mm Hg) compared with NC rats (4.3 ± 0.3 mm Hg). Enalapril treatment (25 mg/kg/day in drinking water) had no effect on nondiabetic rats (NE, n = 8) as compared with untreated NC rats, but significantly improved RIHP response (ΔRIHP) to VE in diabetic rats (DE, n = 9; 2.8 ± 0.5 mm Hg). Both ΔFELi and ΔFEPi were restored by enalapril treatment in diabetic rats and no significant differences were found in ΔFELi and ΔFEPi between DE (ΔFELi = 26.81 ± 4.94{\%} and ΔFEPi = 10.45 ± 4.67{\%}) and NC groups of rats in response to VE. These data suggest that the activated RAS and the decrease in RIHP may play an important role in the increased proximal tubule reabsorption, and the attenuated natriuretic and diuretic responses to acute volume expansion in diabetic rats.",
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