Time-course effects of oral guanethidine administration on cardiovascular and autonomic effects on dogs

The time-course effects of guanethidine (2.5 mb/kg/day, p.o.) administered for 2 days, 7 days and 7-8 months were investigated in dogs. Guanethidine treatment for 2 days failed to produce any significant alterations in sympathetic neuronal activity to the myocardium, resting neurogenic tone in the perfused hind limb vasculature and lumbar sympathetic neuronal transmission. Following guanethidine administration for a peroid of 7 days both cardiac and lumbar sympathetic neuronal activity was markedly and significantly depressed with concomitant reduction in heart rate and resting neurogenic tone to the hind limb. However, continued treatment with guanethidine for a period of 7-8 months resulted in complete restoration of cardiac as well as lumbar sympathetic neuronal activity. Both heart rate and resting neurogenic tone were also returned to placebo levels. The development of tolerance of these sympathetic nerves to guanethidine treatment was not associated with any alterations in the activity of adrenergic receptors. Further, there was a significant and time-dependent increase in cholinergic vasocilator activity in the lumbar sympathetic chain which could account for the exertional hypotension noted in the patients receiving guanethidine treatment.