Opposite effects of chronic cortisol treatment on pre- and postsynaptic actions of clonidine in pithed rats

1. Both clinical and experimental studies have shown that chronic elevation of plasma cortisol levels are attended by altered adrenergic receptor function. In the present study we examined the effects of chronic cortisol treatment (25 mg kg-1 day-1 for 7 days by minipumps) on the peripheral cardiovascular responses of pithed, adrenal demedullated vagotomized rats. 2. Chronic cortisol treated rats had higher basal diastolic blood pressures after being pithed, suggesting that sympathetic outflow is not required to sustain elevated peripheral resistance in glucocorticoid-induced hypertension. 3. Whereas alpha 1-adrenoreceptor-mediated diastolic blood pressure responses were unaltered, alpha 2-adrenoreceptor-mediated vasopressor responses were potentiated in pithed rats which were chronically treated with cortisol. 4. Elevation of plasma noradrenaline induced by the stimulation of the entire sympathetic outflow of pithed rats was not changed but the clonidine-induced presynaptic alpha 2-adrenoreceptor inhibition of noradrenaline release was attenuated by chronic cortisol treatment. 5. In conclusion, in adrenal demedullated pithed rats the responses mediated by peripheral pre- and postjunctional alpha 2-adrenoreceptors appeared to be affected oppositely after chronic cortisol treatment, suggesting that the pharmacologically homogeneous alpha 2-adrenoreceptor population may be modulated differently by chronic elevation of plasma glucocorticoids.