Early Changes in Noradrenaline Content of Some Brain Nuclei in Spontaneously Hypertensive Rats

Abstract

1. The noradrenaline content of individual brain nuclei was measured by using high-pressure liquid chromatography coupled with electrochemical detection.2. This study was performed on spontaneously hypertensive rats during the development of hypertension (4 and 12 weeks) and also on deoxycorticosterone-salt hypertensive rats after 1 and 4 weeks of treatment.3. In young spontaneously hypertensive rats a significant decrease in noradrenaline content was observed in some medullary and hypothalamic nuclei which are involved in cardiovascular regulation. No change was observed after deoxycorticosterone-salt treatment.4. It is proposed that a change in adrenergic activity, restricted to brain cardiovascular centres, could represent a mechanism triggering spontaneous hypertension.

Specific changes in hypothalamic alpha-adrenoceptors in young spontaneously hypertensive rats.

“…However, some reports of agedependent alterations in catecholamine metabolism exist: le Quan Bui ct al. 4 recently described reduced norepinephrine content in some medullary and hypothalamic nuclei in the SHR at 4 but not 12 weeks of age. The alterations in epinephrine concentration 1 and phenylethandamine N-methyltransferase (PNMT) activity" in brain-stem areas described by Saavedra were restricted to younger, 4-week-old SHR.…”

“…31 Hypothalamic a 2 -adrenoceptors have been implicated in the inhibition of central sympathetic outflow." Furthermore, the hypotensive actions of clonidine and a-methyldopa have been explained in terms of their stimulation of central a-adrenoceptors (Scriabine et al, 1 ' Davies and Reid,* 4 Isaac"). The hypothalamus contains a functionally heterogeneous group of adrenergic receptors," and it is likely that the increase in total hypothalamic a,-adrenoceptors we observed in young SHR reflects increases in certain critical areas of the hypothalamus.…”

“…Wijnen et al* showed decreased norepinephrine turnover in discrete hypothalamic nuclei of SHR prior to the development of hypertension, but not in older animals. A reduction in norepinephrine content 4 ' 6 and dopamine /3-hydroxylase" activity in specific nuclei of the hypothalamus was demonstrated as early as 4 weeks after birth in the SHR. Thus, central neural mechanisms are implicated in the onset of hypertension in the spontaneously hypertensive rat.…”

“…12 After washing in isotonic saline at 0°C, the brain regions were homogenized using a Polytron homogenizer in approximately 20 ml of 0. 4 , 0.1% ascorbic acid, pH 7.4. Incubations were terminated by rapid filtration under vacuum through Whatman GF/C glass fiber filters.…”

Decreased Norepinephrine Content in the Medulla Oblongata in Severely Hypertensive Rats

“…However, the results have varied with regard to the CA content and changes in turnover. For example, in some studies the NE content in the medulla oblongata was lower in SHR than in Wistar-Kyoto (WKY) rats (Le Quan-Bui et al 1980;Nomura et al 1985), whereas in other investigations the opposite was true (Versteeg et al 1976;Winternitz et al 1984). Still others showed no differences between SHR and WKY (Saavedra et al 1978;Saavedra 1979).…”