The nigrostriatal dopamine system and the development of hypertension in the spontaneously hypertensive rat. 1995

W de Jong, and A C Linthorst, and H G Versteeg
Institut de Pharmacologie, Strasbourg.

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.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D008297 Male Males
D011918 Rats, Inbred SHR A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke. Rats, Spontaneously Hypertensive,Rats, SHR,Inbred SHR Rat,Inbred SHR Rats,Rat, Inbred SHR,Rat, SHR,Rat, Spontaneously Hypertensive,SHR Rat,SHR Rat, Inbred,SHR Rats,SHR Rats, Inbred,Spontaneously Hypertensive Rat,Spontaneously Hypertensive Rats
D011921 Rats, Inbred WKY A strain of Rattus norvegicus used as a normotensive control for the spontaneous hypertensive rats (SHR). Rats, Wistar Kyoto,Wistar Kyoto Rat,Rats, WKY,Inbred WKY Rat,Inbred WKY Rats,Kyoto Rat, Wistar,Rat, Inbred WKY,Rat, WKY,Rat, Wistar Kyoto,WKY Rat,WKY Rat, Inbred,WKY Rats,WKY Rats, Inbred,Wistar Kyoto Rats
D002421 Caudate Nucleus Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. Caudatus,Nucleus Caudatus,Caudatus, Nucleus,Nucleus, Caudate
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D006719 Homovanillic Acid A 3-O-methyl ETHER of (3,4-dihydroxyphenyl)acetic acid. 3-Methoxy-4-Hydroxyphenylacetic Acid,4-Hydroxy-3-Methoxyphenylacetic Acid,3 Methoxy 4 Hydroxyphenylacetic Acid,4 Hydroxy 3 Methoxyphenylacetic Acid,Acid, 3-Methoxy-4-Hydroxyphenylacetic,Acid, 4-Hydroxy-3-Methoxyphenylacetic,Acid, Homovanillic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013378 Substantia Nigra The black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce DOPAMINE, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored MELANIN is a by-product of dopamine synthesis. Nigra, Substantia,Nigras, Substantia,Substantia Nigras
D015102 3,4-Dihydroxyphenylacetic Acid A deaminated metabolite of LEVODOPA. DOPAC,Homoprotocatechuic Acid,3,4-Dihydroxyphenylacetic Acid, Monosodium Salt,3,4 Dihydroxyphenylacetic Acid

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