Role of the adrenal medulla in the metabolic and pressor actions of 8-OH-DPAT.
1. Intravenous administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 150 micrograms kg-1) into conscious sham-operated rats caused significant increases in basal glycaemia with minor changes in basal insulinaemia. Glucose-stimulated (intravenous glucose tolerance test) plasma insulin levels were significantly inhibited in 8-OH-DPAT-treated sham-operated animals. These metabolic changes were associated with significant and sustained falls in blood pressure (BP) and heart rate (HR) preceded by transient (less than 5 min) increases only in BP. 2. In adrenodemedullated animals, 8-OH-DPAT failed to cause an initial vasoconstriction, hyperglycaemia, or inhibition of glucose-stimulated plasma insulin despite eliciting falls in BP and HR that were comparable to those observed in sham-operated animals. 3. Noradrenaline, adrenaline and dopamine levels in the adrenal tissue were reduced by about 95% in adrenodemedullated rats as compared to sham-operated rats. A functionally intact adrenal cortex was indicated by the presence of corticosterone in the plasma of both adrenodemedullated and sham-operated rats. 4. The present data demonstrate that 8-OH-DPAT mediates an initial increase in BP and changes in metabolic parameters via intact adrenal medulla and may thus be consequential to the release of adrenaline, whereas the sustained cardiovascular effects of 8-OH-DPAT are not.
Bouhelal
R
R
Preclinical Research, Sandoz Pharma AG, Basel, Switzerland.
Mir
A K
AK
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000302:Adrenal Cortex / Q000502:physiology*; D000313:Adrenal Medulla / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D005951:Glucose Tolerance Test / Q000379:methods; D006339:Heart Rate / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D001786:Blood Glucose; D002395:Catecholamines; D007328:Insulin; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003345:Corticosterone