Neuronal and postjunctional components in the blood pressure effects of dopamine and bromocriptine in rabbits.
We have studied the contribution of neuronal and postjunctional dopamine (DA) receptors and of the DA1 and DA2 receptor subtypes to the blood pressure effects of DA and bromocriptine in the rabbit. The norepinephrine release rate, i.e., the rate of entry of endogenous norepinephrine into the plasma, was derived from the plasma level of endogenous norepinephrine and the plasma [3H]norepinephrine clearance. Bromocriptine (40 micrograms kg-1) lowered the norepinephrine release rate and the arterial blood pressure both in anesthetized rabbits and in pithed rabbits with electrically stimulated sympathetic outflow. These effects were antagonized by the selective DA2 antagonist domperidone but not by the selective DA1 antagonist SCH 23390. DA (10-160 micrograms kg-1 min-1) dose-dependently increased the norepinephrine release rate and caused only transient hypotension in anesthetized rabbits. However, after treatment with desipramine, DA did not change the norepinephrine release rate and produced a persistent fall in blood pressure. When DA and domperidone were given simultaneously to desipramine-treated rabbits, the hypotensive effect of DA was unchanged, but now DA increased the norepinephrine release rate. When DA and SCH 23390 were given simultaneously to desipramine-treated rabbits, DA failed to lower blood pressure and decreased the norepinephrine release rate. Propranolol did not change the effects of DA in desipramine-treated rabbits. These results suggest that bromocriptine decreases blood pressure by activating ganglionic and/or prejunctional, inhibitory DA2 receptors in the peripheral sympathetic nervous system. DA also activates these receptors, but in addition releases norepinephrine in the manner of an indirectly acting sympathomimetic amine and activates postjunctional vascular DA1 receptors, and the latter seems to be the main component in DA-induced hypotension.
Ensinger
H
H
Majewski
H
H
Hedler
L
L
Starke
K
K
D000758:Anesthesia; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001971:Bromocriptine / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D003655:Decerebrate State; D003891:Desipramine / Q000494:pharmacology; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D005260:Female; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*
D001552:Benzazepines; D011954:Receptors, Dopamine; D017981:Receptors, Neurotransmitter; D009599:Nitroprusside; D001971:Bromocriptine; D004294:Domperidone; D011433:Propranolol; D003000:Clonidine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine