Differential effects of .ALPHA.-methyldopa, clonidine and hydralazine on norepinephrine and epinephrine synthesizing enzymes in the brainstem nuclei of spontaneously hypertensive rats.
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Repeated administrations of clonidine to spontaneously hypertensive rats (SHR) markedly lowered dopamine β-hydroxylase (DBH) activity in the locus coeruleus (LC) and increased it in the spinal intermediolateral cell column (IML), while α-methyldopa tended to lower the enzyme activity in the medullary nucleus tractus solitarii (NTS) and Al cell areas. Clonidine-induced inhibition of <SUP>3</SUP>H-norepinephrine binding to crude cerebral membranes of SHR or Kyoto Wistar rats (KWR) as a measure of α-receptor agonist activity was 7 times greater than that of (±) a-methyl- (±) -norepin-ephrine. Clonidine and hydralazine significantly lowered phenylethanolamine N-methyltransferase (PNMT) activity elevated in the nucleus hypothalamicus posterior (NHP) of SHR to the level of KWR, and both drugs or α-methyldopa consistently increased PNMT in the nucleus paraventricularis (NPA). Peripherally active hydralazine also increased PNMT activity in the NTS, and antagonized the activity elevated in the Al cell area of SHR to the level of KWR. In conclusion, clonidine selectively lowers DBH activity in the LC, while α-methyldopa appears to decrease the enzyme activity in the medullary NTS and Al cell areas, suggesting different sites of action of both drugs. The decreased DBH activity in these nuclei may be related to stimulation of respective α-noradrenergic receptors. Elevating effects of all three drugs on PNMT activity in the NPA may be due to decreased baroreceptor afferent impulses to the nucleus after a fall in blood pressure.
- 公益社団法人 日本薬理学会の論文
公益社団法人 日本薬理学会 | 論文
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