THE NIGROSTRIATAL DOPAMINE SYSTEM - ROLE IN THE DEVELOPMENT OF HYPERTENSION IN SPONTANEOUSLY HYPERTENSIVE RATS

The effects of lesions in the pars compacta of the substantia nigra of 4-week-old spontaneously hypertensive rats (SHR) and normotensive Wis tar-Kyoto rats (WKY) were studied on (a) changes in blood pressure dur ing a period of 6 weeks following lesioning, and (b) dopamine and meta bolite concentrations in the caudate nucleus and (c) the in vitro rele ase of [H-3]dopamine from caudate nucleus slices 6 weeks after the les ioning. We report here that substantia nigra lesions caused a profound attenuation of the development of hypertension in SHR. No effect on h eart rate was observed. Whereas the concentrations of dopamine and 3,4 -dihydroxyphenylacetic acid (DOPAC) in the caudate nucleus were not di fferent, the amount of homovanillic acid (HVA) and the ratios DOPAC/do pamine and HVA/dopamine were lower in sham-treated SHR than in sham-tr eated WKY, indicating a lower turnover of dopamine in SHR. Six weeks a fter lesioning, the concentrations of dopamine, DOPAC and HVA were dec reased in the caudate nucleus (46-66%) of both strains, whereas DOPAC/ dopamine and HVA/dopamine ratios tended to be increased in both SHR an d WKY. Using an in vitro superfusion method, it was found, that the el ectrically stimulated release of [H-3]dopamine from caudate nucleus sl ices of sham-treated SHR was lower than from slices of sham-treated WK Y at the age of 10 weeks. Six weeks after lesioning, the stimulus-evok ed release of [H-3]dopamine from the remaining terminals was significa ntly increased in caudate nucleus slices of SHR, whereas the differenc e did not reach statistical significance in WKY. Considering that the release of dopamine from terminals in the caudate nucleus of substanti a nigra-lesioned SHR is similar to that of sham-treated WKY, we postul ate that this normalization of dopaminergic-activity might be the caus al factor underlying the attenuation of the development of hypertensio n in SHR after bilateral lesioning of the substantia nigra.