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 Wistar-Kyoto rats (WKY) were studied on (a) changes in blood pressure during a period of 6 weeks following lesioning, and (b) dopamine and metabolite concentrations in the caudate nucleus and (c) the in vitro release of [3H]dopamine from caudate nucleus slices 6 weeks after the lesioning. We report here that substantia nigra lesions caused a profound attenuation of the development of hypertension in SHR. No effect on heart rate was observed. Whereas the concentrations of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in the caudate nucleus were not different, the amount of homovanillic acid (HVA) and the ratios DOPAC/dopamine and HVA/dopamine were lower in sham-treated SHR than in sham-treated WKY, indicating a lower turnover of dopamine in SHR. Six weeks after lesioning, the concentrations of dopamine, DOPAC and HVA were decreased in the caudate nucleus (46-66%) of both strains, whereas DOPAC/dopamine and HVA/dopamine ratios tended to be increased in both SHR and WKY. Using an in vitro superfusion method, it was found, that the electrically stimulated release of [3H]dopamine from caudate nucleus slices of sham-treated SHR was lower than from slices of sham-treated WKY at the age of 10 weeks. Six weeks after lesioning, the stimulus-evoked release of [3H]dopamine from the remaining terminals was significantly increased in caudate nucleus slices of SHR, whereas the difference did not reach statistical significance in WKY.(ABSTRACT TRUNCATED AT 250 WORDS)
Linthorst
A C
AC
Department of Medical Pharmacology, Rudolf Magnus Institute, Medical Faculty, University of Utrecht, The Netherlands.
van Giersbergen
P L
PL
Gras
M
M
Versteeg
D H
DH
de Jong
W
W
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002421:Caudate Nucleus / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology; D006719:Homovanillic Acid / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D017072:Neostriatum / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013378:Substantia Nigra / Q000503:physiopathology*
D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid