RGD Reference Report - Hepatic heme and drug metabolism in rats with chronic mountain sickness. - Rat Genome Database

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Hepatic heme and drug metabolism in rats with chronic mountain sickness.

Authors: Bonkovsky, HL  Lincoln, B  Healey, JF  Ou, LC  Sinclair, PR  Muller-Eberhard, U 
Citation: Bonkovsky HL, etal., Am J Physiol. 1986 Oct;251(4 Pt 1):G467-74.
RGD ID: 1626356
Pubmed: PMID:3094379   (View Abstract at PubMed)

Rats chronically exposed to hypobaric conditions develop pulmonary hypertension, right heart failure, hemoglobinemia, and in preliminary studies were recently found to have increased hepatic cytochrome P-450 content and activity of heme oxygenase, the rate-limiting enzyme for heme breakdown. To further delineate effects of chronic hypoxic, hypobaric exposure, on hepatic physiology and biochemistry, we have studied heme and drug metabolism in male Sprague-Dawley rats exposed to hypoxic conditions for 4-5 wk. Hypoxia, produced by exposure of rats to room air under hypobaric conditions (approximately 380 Torr), caused marked polycythemia [hematocrit (Hct) 70% vs. control Hct 43%], plasma hemoglobinemia, depletion of plasma haptoglobin, and decreased hemopexin concentrations. It also led to significant (20-30%) increases in concentrations of total hepatic heme and microsomal cytochrome P-450 and increased activities of heme oxygenase. In contrast, activity of 5-aminolevulinate synthase, the rate-limiting enzyme of hepatic heme synthesis, was significantly decreased in hypoxic rats and was not as inducible as in control normoxic rats. Hypoxia did not alter the rest of the heme synthetic pathway, as shown by a normal rate of conversion of 5-aminolevulinate to heme. Hypoxic exposure had no effect on the concentration of hepatic cytochrome-b5 but decreased activity of NADPH-cytochrome c reductase. Rates of metabolism of aminopyrine, benzphetamine, ethoxyresorufin, and warfarin were similar in hepatic microsomes obtained from hypoxic and normoxic rats. Thus the oxygen-requiring processes of hepatic heme and drug metabolism were well maintained despite chronic profound hypoxia sufficient to cause cardiopulmonary complications.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hypoxia  ISOHp (Rattus norvegicus)1626356; 1626356protein:decreased expression:plasmaRGD 
Hypoxia  IEP 1626356protein:decreased expression:plasmaRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to hypoxia  IEP 1626356 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hp  (haptoglobin)

Genes (Mus musculus)
Hp  (haptoglobin)

Genes (Homo sapiens)
HP  (haptoglobin)


Additional Information