Stimulation of Peripheral Dopamine Receptors in Rats: A Mechanism for Novel Antihypertensive Agents

Abstract

1. The aim of this investigation was to provide support for the hypothesis that stimulation of peripheral dopamine receptors reduces sympathetic vasomotor tone and thus may be a mechanism for novel antihypertensive agents. 2. NN-Di-n-propyldopamine (DPDA: 0.03-0.1 mg min−1 kg−1 intra-arterially) produced sustained decreases in blood pressure measured from the cannulated tail artery in conscious spontaneously hypertensive rats. 3. This antihypertensive action of DPDA was antagonized by sulpiride but not by atropine, promethazine, propranolol or indomethacin. 4. DPDA failed to lower blood pressure in spontaneously hypertensive rats in which peripheral stores of catecholamines had been previously depleted with syrosingopine. 5. In the pithed atropine-pretreated spontaneously hypertensive rats in which the low blood pressure was elevated by electrical stimulation of the spinal cord, DPDA produced hypotensive effects which were antagonized by sulpiride. However, DPDA, in contrast to phentolamine, did not modify the blood pressure raised by an infusion of adrenaline. 6. In conclusion, the blood pressure-lowering action of DPDA is due to stimulation of dopamine receptors which decreases noradrenaline release and consequently sympathetic vasomotor tone. These receptors may be located on sympathetic ganglia or sympathetic endings innervating resistance vessels.