Diabetes induces sex-dependent changes in neuronal nitric oxide synthase dimerization and function in the rat gastric antrum

Pandu R R Gangula, William L. Maner, Maria Micci, Robert E. Garfield, Pankaj Jay Pasricha

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Diabetic gastroparesis is a disorder that predominantly affects women. However, the biological basis of this sex bias remains completely unknown. In this study we tested the hypothesis that a component of this effect may be mediated by the nitrergic inhibitory system of the enteric nervous system. Age-matched male and female Sprague-Dawley rats were studied 8 or 12 wk after streptozotocin (55 mg/kg body wt ip)-induced sustained hyperglycemia and compared with controls. Solid gastric emptying (GE) studies were performed in all the groups. Changes in gastric antrum neuronal nitric oxide synthase (nNOS) mRNA and protein levels were analyzed by real-time PCR and Western immunoblotting, respectively. nNOS dimerization studies were performed using low-temperature SDS-PAGE. In vitro nitrergic relaxation (area under curve/mg tissue wt) was studied after the application of electric field stimulation in an organ bath. Changes in intragastric pressure (mmHg·s) in freely moving rats in the presence or absence of NGnitro-L-arginine methyl ester (nitric oxide synthase inhibitor) were examined by an ambulatory telemetric method. After diabetes induction, GE is delayed in both male and female rats. However, diabetic females exhibited significant delayed GE than in diabetic males. Compared with male controls, gastric nNOS expression and nitrergic relaxation were substantially elevated in healthy female control rats, accompanied by significantly reduced intragastric pressure. The active dimeric form and dimer-to-monomer ratio of nNOSα were also higher in healthy females compared with male rats (P < 0.05). Diabetic females, but not males, showed significant (P < 0.05) impairment in both gastric nNOSα dimerization and nitrergic relaxation, accompanied by an increase in intragastric pressure. Our data provide evidence that females may have a greater dependency on the nitrergic mechanisms in health. Furthermore, diabetes seems to affect the nitrergic system to a greater extent in females than in males. Together, these changes may account for the greater vulnerability of females to diabetic gastric dysfunction.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume292
Issue number3
DOIs
StatePublished - Mar 2007

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Pyloric Antrum
Nitric Oxide Synthase Type I
Dimerization
Gastric Emptying
Stomach
Pressure
Gastroparesis
Enteric Nervous System
Sexism
Streptozocin
Baths
Nitric Oxide Synthase
Hyperglycemia
Electric Stimulation
Area Under Curve
Sprague Dawley Rats
Real-Time Polymerase Chain Reaction
Polyacrylamide Gel Electrophoresis
Western Blotting
Messenger RNA

Keywords

  • Intragastric pressure
  • Nitrergic relaxation
  • Solid gastric emptying

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Diabetes induces sex-dependent changes in neuronal nitric oxide synthase dimerization and function in the rat gastric antrum. / Gangula, Pandu R R; Maner, William L.; Micci, Maria; Garfield, Robert E.; Pasricha, Pankaj Jay.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 292, No. 3, 03.2007.

Research output: Contribution to journalArticle

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