Studies on Hypertension : Catecholamine Metabolism in Adrenal Glands and Brain of Spontaneously Hypertensive Rat and Metabolism of Tritium Labeled 3, 4-Dihydroxyphenylalanine in Spontaneously Hypertensive Rat treated with Reserpine, α-Methyl DOPA or 2- (2, 6-Dichlorophenylamino) -2-Imidazoline Hydxochloride

Abstract

In order to analyse the pathogenesis of hypertension, spontaneously hypertensive rats (SHR) were compared with normotensive Wistar strain rats at the age of 8-10 weeks and over the 6 months. Endogenous catecholamine in adrenal glands and brain were determined in the young and adult animals. The levels of tritium labeled 3, 4-hydroxyphenylalanine (³H-DOPA), ³H-dopamine and ³H-noradrenaline in brain stem were determined at various time such as 1, 6 and 12 hours after administration of ³H-DOPA in adult SHR and control Wistar strain rats.
The other experiments were made by comparing the ³H-DOPA metabolism in SHR treated with reserpine, α-methyl DOPA or 2- (2, 6-dichlorophenylamino) -2-imidazoline hydrochloride [ST-155] with control SHR over the 4 months of age.
1) The blood pressure and catecholamine levels in the adrenal glands were higher in SHR than control Wistar strain rats at 8-10 weeks or over 6 months of age.
2) The noradrenaline content was decreased in brain stem of SHR, but was increased in hemispherium and celleberum of them compared with control Wistar strain rats over 6 months of age.
3) Biosynthesis of ³H-dopamine, ³H-noradrenaline in brain stem of SHR after administration of ³H-DOPA was compared with those of Wistar strain rats. The levels of ³H-DOPA, ³H-dopamine and ³H-noradrenaline were lower in SHR than Wistar strain rats at 1 or 6 hours after administration of ³H-DOPA. The observed decrease of DOPA uptake and catecholamine synthesis in brain stem were considered as suggesting upon the relation to the pathogenesis of hypertension.
4) Reserpinized SHR showed higher level of ³H-DOPA in brain and heart, but showed lower level of ³H-dopamine, ³H-noradrenaline and ³H-adrenaline in brain, heart and particularly in adrenal glands.
It is considered that the uptake of ³H-dopamine and synthesis of ³H-catecholamine were inhibited in each organs, and the process from DOPA to dopamine was inhibited in brain and heart of SHR treated with reserpine.
5)³H-DOPA of each organs (brain, heart and adrenal glands) showed higher levels, but ³H-dopamine and ³H-noradrenaline showed lower levels in SHR treated with α-methyl DOPA. It is considered that α-methyl DOPA inhibits the metabolic process of DOPA to dopamine, and replaces and releases catecholamine in each tissue.
6) ³H-DOPA, ³H-dopamine, ³H-noradrenaline and ³H-adrenaline (especially in adrenal glands) in brain, heart and adrenal glands showed no change in SHR treated with ST-155.
It is considered that ST-155 does not influence catecholamine metabolism.