Compromised regulation of the rat brain parenchymal arterioles in vasopressin‐associated acute hyponatremia

Arachidonic acid (AA) is metabolized by the cytochrome P-450 (P-450) epoxygenase pathway to epoxyeicosatrienoic acids (EETs) in the brain parenchymal tissue and perivascular astrocytes. EETs dilate cerebral microvessels and enhance K+ current in cerebrovascular smooth muscle cells. In the current study, the effect of a subdural administration of miconazole, an inhibitor of P-450 epoxygenase, on microvascular perfusion of rat cerebral cortex was evaluated using laser-Doppler flowmetry (LDF) Baseline cerebral blood flow (CBF) decreased by 29.7 +/- 7.3% (n = 5) after administration of 20 microM miconazole into the subdural space for 30 min. Responses of CBF to sodium nitroprusside and 5-hydroxytryptamine were unaltered by miconazole treatment. Administration of vehicle alone in time-control experiments had no effect on CBF. In other experiments, the effects of miconazole on the metabolism of [14C]AA by cultured rat astrocytes and on nitric oxide synthase activity in homogenates of rat brain were examined. Miconazole inhibited conversion of AA to EETs by cultured astrocytes but had no effect on the conversion of L-arginine to L-citrulline by homogenates of rat brain. These results implicate endogenous P-450 epoxides of AA in the regulation of basal blood flow in cerebral microcirculation.

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Effect of acute hyponatremia on rat brain pH and rat brain buffering

AJP Renal Physiology ◽

10.1152/ajprenal.1989.256.1.f113 ◽

1989 ◽

Vol 256 (1) ◽

pp. F113-F119 ◽

Cited By ~ 4

Author(s):

S. Adler ◽

V. Simplaceanu

Keyword(s):

Nuclear Magnetic Resonance ◽

Magnetic Resonance ◽

Rat Brain ◽

31P Nmr ◽

Sodium Concentration ◽

Plasma Sodium ◽

Plasma Sodium Concentration ◽

Brain Ph ◽

Acute Hyponatremia ◽

Sodium Solution

Acute hyponatremia was induced in rats by subcutaneous pitressin and intraperitoneal injection of 17.5 ml of 2.5% dextrose three times over 2 days. Brain pH was measured by use of 31P-nuclear magnetic resonance (31P-NMR). Two-hour infusion of a 500 meq sodium solution raised plasma sodium concentration (PNa) from 124.6 to 147 meq/l. Brain pH rose 0.1 pH units in the absence of changes in phosphocreatine or ATP. By contrast, increasing PNa in normal rats from 141 to 158 meq/l did not affect brain pH. Brain buffering was examined by 58-min exposure to 20% CO2 followed by a 38-min recovery. Intrinsic brain buffering (Bi) in hyponatremic and normal rats following 15 min of CO2 was similar, 49.1 and 45.5, respectively. After the next 40 min of CO2 exposure Bi was unchanged in hyponatremic rats at 45.8 but increased in controls to 102.5. In recovery Bi was higher initially in controls and rose significantly only in the controls. These results are consistent with the hypothesis that acute hyponatremia impairs the function of the Na+-H+ exchanger in brain.

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Na+-K+-ATPase pump function in rat brain synaptosomes is different in males and females

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1989.257.2.e284 ◽

1989 ◽

Vol 257 (2) ◽

pp. E284-E289 ◽

Cited By ~ 11

Author(s):

C. L. Fraser ◽

P. Sarnacki

Keyword(s):

Rat Brain ◽

Binding Capacity ◽

Binding Studies ◽

Rat Brain Synaptosomes ◽

Maximum Binding Capacity ◽

Brain Synaptosomes ◽

Males And Females ◽

The Difference ◽

Acute Hyponatremia ◽

Na Uptake

To understand the increased morbidity and mortality associated with acute hyponatremia in young women, we characterized the Na+-K+-adenosinetriphosphtase (ATPase) pump in rat brain synaptosomes to determine if this adaptive mechanism was different between the sexes. Veratridine-stimulated sodium (Na+) uptake was significantly greater (P less than 0.001) in females than in males (8.08 +/- 0.3 vs. 5.56 +/- 0.4 nmol/mg protein), suggesting either an increased rate of Na+ uptake and/or decreased extrusion of Na+ by the Na+-K+-ATPase pump in females. Uptake rate was determined by measuring Na+ transport at 5 s, and it was found to be twice as large in females as in males (1.01 +/- 0.2 vs. 0.46 +/- 0.1 nmol/mg protein). However, in the presence of 2.5 mM ouabain, uptake in both groups were similar, suggesting that the difference was probably due to decreased function of the Na+-K+-ATPase pump in females. Transport evaluation of the Na+-K+-ATPase pump showed ouabain-sensitive K+ uptake in males to be significantly greater (P less than 0.001) than in females (10.53 vs. 4.97 nmol/mg protein), and ouabain-sensitive Na+ uptake in inverted synaptosomes was 70% greater in males (4.00 vs. 2.37 nmol/mg protein). [3H]ouabain binding studies showed maximum binding capacity in males and females to be similar (103 +/- 12 vs. 110 +/- 15 pmol/mg protein), whereas the dissociation constant was significantly (P less than 0.005) greater in males (109 +/- 8 vs. 82 +/- 6 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

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