The nigrostriatal dopamine system and the development of hypertension in the spontaneously hypertensive rat

Several observations reported in the literature reveal a role of brain catecholaminergic systems in the development of hypertension in spontaneously hypertensive rats (SHR). As reviewed here, our results obtained with intracerebroventricular injections of 6-hydroxydopamine in your SHR point in particular to the involvement of the nigrostriatal dopamine system. The electrically stimulated release of radiolabeled dopamine in vitro from caudate nucleus slices of SHR was lower than that in slices of normotensive Wistar-Kyoto rats (WKY). Using an in vivo microdialysis method, we found that the extracellular concentration of dopamine and the metabolite DOPAC was lower in the caudate nucleus of conscious SHR than in that of WKY. We also studied the effects of lesions of the pars compacta of the substantia nigra of 4 week-old SHR and WKY, 1) on blood pressure and heart rate, 2) on the concentrations of dopamine and metabolites in the caudate nucleus and 3) on the release of radiolabeled dopamine from caudate nucleus slices using an in vitro superfusion method, 6 weeks following lesioning. Substantia nigra lesions caused a profound attenuation of the development of hypertension in SHR, with no effect on heart rate. The ratios DOPAC/dopamine and HVA/dopamine were lower in sham-treated SHR than in sham-treated WKY pointing to a lower turnover of dopamine in SHR. Six weeks after lesioning, the concentrations of dopamine were decreased in the caudate nucleus of both strains. At this time, the stimulus-evoked release of dopamine from the remaining terminals was significantly increased in caudate nucleus slices of SHR but not in slices of WKY. Thus, whereas the release of dopamine from caudata nucleus slices is lower in sham-treated SHR than in sham-treated WKY, lesioning of the substantia nigra results in a similar release of dopamine from caudate nucleus slices of lesioned SHR and sham-treated WKY. This normalization of dopaminergic activity may be the causal factor underlying the attenuation of the development of hypertension in SHR after bilateral lesioning of the pars compacta, of the substantia nigra.