title: Role of dopamine in the development of spontaneous hypertension.
abstract: 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.
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006892:Hydroxydopamines / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D001596:Benzylamines; D006892:Hydroxydopamines; C012102:DSP 4; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine