Role of dopamine in the development of spontaneous hypertension

To investigate the role of brain catecholamines in the development of spontaneous hypertension, rats were treated with different doses of the neurotoxins 6-hydroxydopamine (6-OHDA) or DSP-4 (N-[2-chloroethyl]-N-ethyl-2-bromobenzylamine hydrochloride). Intracerebroventricular (i.c.v.) 6-OHDA attenuated the development of hypertension in spontaneously hypertensive rats (SHR) and also lowered the systolic blood pressure (BP) in Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Norepinephrine was markedly and dose-dependently depleted in brain areas of all three substrains. Dopamine was affected also, although to a lesser extent. Pretreatment with the norepinephrine-uptake inhibitor desmethylimipramine (DMI) did not influence the effect of 6-OHDA on the development of hypertension in SHR. DMI largely antagonized the 6-OHDA-induced depletion of brain norepinephrine, while dopamine depletion was not affected. Specific depletion of brain norepinephrine by treatment with DSP-4 did not alter the rise in BP in SHR. These results suggest that the effect of 6-OHDA on the development of hypertension in SHR may not be mediated through destruction of brain norepinephrine neurons, but that interruption of brain dopaminergic mechanisms is a possibility in this respect.