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.