Role of the adrenal gland in the metabolic and cardiovascular effects of 8-OH-DPAT in the rat.
In the present study, the role of the adrenal gland in the hypoinsulinaemic and hyperglycaemic effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) vis-à-vis the cardiovascular effects were examined using adrenalectomized and sham-operated (with intact adrenals) Sprague-Dawley rats. Intravenous administration of 8-OH-DPAT (150 micrograms/kg) into conscious sham-operated animals caused significant increases in basal plasma glucose levels without any change in basal plasma insulin levels whereas glucose-stimulated plasma insulin levels were markedly inhibited. These 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. In adrenalectomized animals, 8-OH-DPAT-mediated initial vasoconstriction, hyperglycaemia and inhibition of evoked plasma insulin levels were abolished. However, in these animals, 8-OH-DPAT produced falls in BP and HR that were comparable to those observed in sham-operated animals. Plasma corticosterone was increased 15 min after 8-OH-DPAT in sham-operated animals whereas it was undetectable in adrenalectomized animals. The data indicate that unlike the effects of 8-OH-DPAT to decrease BP and HR, the initial increase in BP and its effects on the metabolic parameters are clearly dependent on intact adrenals.
Bouhelal
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Sandoz Ltd., Preclinical Research, Basel, Switzerland.
Mir
A K
AK
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000311:Adrenal Glands / Q000502:physiology*; D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D005951:Glucose Tolerance Test; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007328:Insulin / Q000097:blood*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003345:Corticosterone