Pressor responses to brain dopaminergic stimulation.
1. Systemic administration of a dopamine D2 receptor agonist, such as quinpirole, causes a centrally mediated rise in blood pressure (BP) with a maximum at 1-2 min after injection. At 30 min after injection, when BP has returned to baseline, further treatment with these drugs has little effect on BP. Moreover, the antihypertensive effects of sympathoinhibitory drugs, such as clonidine and rilmenidine, is markedly inhibited. Increased circulating levels of vasopressin contribute to the initial rise in BP, but return to baseline thereafter. Differential changes in sympathetic vasomotor tone may be involved in the apparent desensitization induced by quinpirole. 2. Stimulation of the region of origin of the mesolimbic dopamine (DA) system in the brain, the ventral tegmental area, causes a long-lasting increase in BP. In this model, circulating levels of vasopressin are moderately increased through a non-dopaminergic mechanism. Dopaminergic stimulation causes a functional potentiation of the effect of vasopressin, resulting in an increase in BP. 3. Spontaneously hypertensive rats (SHR) display several changes in central dopaminergic responses. Dopamine levels in the brain are normal, while resting DA activity appears reduced. Partial depletion of forebrain DA levels, particularly in the nigrostriatal system, causes an inhibition of the development of hypertension and normalizes deficient functional responses to dopaminergic drugs in the SHR. 4. These results show that brain DA is involved in several aspects of cardiovascular regulation and may be involved in the development of hypertension. The widespread involvement of brain DA systems in behavioural, hormonal and cardiovascular mechanisms suggests that these systems play an important role in the integration of stress and environmental stimuli with homeostatic mechanisms in the body.
van den Buuse
M
M
Baker Medical Research Institute, Prahran, Victoria, Australia. maarten.vandenbuuse@baker.edu.au
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology
D018491:Dopamine Agonists; D011954:Receptors, Dopamine