PRESSOR-RESPONSES TO BRAIN DOPAMINERGIC STIMULATION

1. Systemic administration of a dopamine D-2 receptor agonist, such as quinpirole, causes a centrally mediated rise in blood pressure (BP) w ith a maximum at 1-2 min after injection. At 30 min after injection, w hen BP has returned to baseline, further treatment with these drugs ha s little effect on BP. Moreover, the antihypertensive effects of sympa thoinhibitory drugs, such as clonidine and rilmenidine, is markedly in hibited. Increased circulating levels of vasopressin contribute to the initial rise in BP, but return to baseline thereafter. Differential c hanges in sympathetic vasomotor tone may be involved in the apparent d esensitization induced by quinpirole. 2. Stimulation of the region of origin of the mesolimbic dopamine (DA) system in the brain, the ventra l tegmental area, causes a long-lasting increase in BP. In this model, circulating levels of vasopressin are moderately increased through a nondopaminergic mechanism. Dopaminergic stimulation causes a functiona l potentiation of the effect of vasopressin, resulting in an increase in BP. 3. Spontaneously hypertensive rats (SHR) display several change s in central dopaminergic responses. Dopamine levels in the brain are normal, while resting DA activity appears reduced. Partial depletion o f forebrain DA levels, particularly in the nigrostriatal system, cause s an inhibition of the development of hypertension and normalizes defi cient functional responses to dopaminergic drugs in the SHR. 4. These results show that brain DA is involved in several aspects of cardiovas cular regulation and may be involved in the development of hypertensio n. The widespread involvement of brain DA systems in behavioural, horm onal 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.