Cardiovascular responsiveness to sympathetic activation after chronic epinephrine administration

The effects of chronic elevation of plasma epinephrine concentrations on pressor and cardiac chronotropic responses to spinal stimulation and exogenous norepinephrine were studied in the pithed rat. Animals were treated s.c. with epinephrine (100 micrograms/kg/hr) or vehicle for 6 days. Treatment with epinephrine resulted in hypertension. Epinephrine treatment significantly reduced pressor and cardiac chronotropic responses to norepinephrine. This treatment also reduced cardiac chronotropic responses to spinal stimulation but had no significant effect on pressor responses to spinal stimulation. The preferential beta-2 adrenoceptor antagonist ICI 118,551 (50 micrograms/kg) had no effect on pressor or cardiac chronotropic responses to norepinephrine in either vehicle-treated or epinephrine-treated animals. Similarly, pressor responses to spinal stimulation were unaffected in the vehicle-treated group. However, ICI 118,551 significantly reduced pressor responses to spinal stimulation after epinephrine treatment. Chronic epinephrine treatment also resulted in accumulation of epinephrine in the heart, kidneys and aorta. However, epinephrine accumulation in the heart was much greater than in the kidney or aorta. Acute infusion of epinephrine, which produced plasma epinephrine concentrations similar to those observed in the chronically treated animals, caused a reduction of pressor and cardiac chronotropic responses to both nerve stimulation and norepinephrine. In conclusion, chronic epinephrine treatment led to accumulation of epinephrine in peripheral tissues and to the development of a facilitatory influence of beta-2 adrenoceptors on pressor responses to nerve stimulation in the pithed rat that were not observed in vehicle-treated animals. The authors believe that this influence is prejunctional in nature.(ABSTRACT TRUNCATED AT 250 WORDS)