Sex differences result in increased morbidity from hyponatremia in female rats.
The development of symptomatic hyponatremia in otherwise healthy young women can result in death or permanent brain damage. The reasons for the increased female susceptibility to complications from hyponatremia are, however, unclear. To determine whether mechanisms that normally defend the brain against damage from hyponatremia are less effective in females than males, we studied both sodium transport in the brains of hyponatremic male and female rats and the effects of parenteral arginine vasopressin on brain high-energy phosphate metabolism and intracellular pH. Basal sodium uptake in synaptosomes prepared from whole brain of females (2.20 nmol/mg protein) and males (2.98 nmol/mg protein) was not statistically different. In contrast, veratridine-stimulated sodium uptake in female brain was 8.20 nmol/mg protein, which was 86% greater (P less than 0.001) than the 6.12 nmol/mg protein observed for male brain. Additionally, sodium uptake between 5 and 60 s was significantly (P less than 0.001) greater in females than males. These data suggest that the Na+-K+-adenosinetriphosphatase (ATPase) pump function in female rat brain synaptosomes is less effective than in males. To determine whether arginine vasopressin, a peptide hormone that promotes water retention by the kidney, had any effects on cerebral energy metabolism, we performed phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) studies on the brain of normonatremic young adult male and female rats subjected to high (20 IU) peripheral doses of arginine vasopressin. We found decreased high-energy phosphate generation, elevated inorganic phosphate, and intracellular acidosis after arginine vasopressin administration in females but not males.(ABSTRACT TRUNCATED AT 250 WORDS)
Fraser
C L
CL
Department of Medicine, Veterans Administration Medical Center, San Francisco 94121.
Kucharczyk
J
J
Arieff
A I
AI
Rollin
C
C
Sarnacki
P
P
Norman
D
D
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001693:Biological Transport, Active; D001921:Brain / Q000378:metabolism*; D001929:Brain Edema / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D007010:Hyponatremia / Q000150:complications / Q000503:physiopathology*; D008297:Male; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism
D010725:Phosphocreatine; D001127:Arginine Vasopressin; D000255:Adenosine Triphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase