Responses of adrenal catecholamine secretion to lateral hypothalamic stimulation and lesion in rats

Brain Research, 363 (1986) 141-144

141

Elsevier BRE 21273

Short Communications

Responses of adrenal catecholamine secretion to lateral hypothalamic stimulation and lesion in rats TOSHIHIKO KATAFUCHI1, HIRONOBU YOSHIMATSU l , YUTAKA OOMURA 1and AKIO SATO2

IDepartment of Physiology, Faculty of Medwme, Kyushu Umverszty60, Fukuoka 812 and 2Department of Physiology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173 (Japan) (Accepted August 20th, 1985)

Key words" lateral hypothalamlc area - - stlmulat]on - - lesion - - adrenal eatecholamme secretion - - rat

The effects of electrical stimulation and lesion of the lateral hypothalam]c area (LHA) on catecholamme (CA) secreUon from the adrenal medulla were investigated in anestheuzed rats. A differential secreUon of epinephrine (E) and norepmephrme (NE) was observed, in which a single stimulating site could produce different effects on E and NE secretion On the basis of change m the E secretion rate during stimulation, stimulation sites could be classified into 3 groups: group A which showed increase m E secreuon (no change m NE), group B which showed decrease in E (and also decrease in NE), and group C wh]ch showed no change in E (but a decrease in NE) No relationship was observed between the sites of stimulation m the LHA and the direction of the responses Les~onsof the stimulation sites decreased CA secretion to different extent among the three groups and these differences could be predicted by the effects of stimulation at the same sites. These results suggest that the LHA has both faclhtatory and mh]bltory effects on the sympatho-adrenal function and that the former ~spredominant. The lateral hypothalamic area ( L H A ) has been shown to be implicated in the regulation of the homeostasis of energy metabolism and relevant hormonal secretion by the autonomic nervous system2.9A2A3,15. Anatomical evidence demonstrating neural projections from the L H A to the sympathetic preganglionic neuron in the spinal cord in the ratH has reinforced the functional relationship between the L H A and sympatho-adrenal system. However, effects of electrical stimulation of the hypothalamus on catecholamine (CA) secretion into the adrenal vein have been reported exclusively from experiments on cats and dogs3-SA0. We have already studied the effects'of the ventromedial hypothalamic ( V M H ) lesion on C A secret]on from the adrenal medulla in rats 16. The present study was u n d e r t a k e n to investigate the responses of adrenal C A secretion to stimulation and lesions of the L H A in anesthetized rats. Fifteen male adult Wistar rats weighing 250-300 g

were used. U n d e r ketamine anesthesia (100 mg/kg), concentric bipolar electrodes (outer, 26-gauge stainless-steel tube; inner, 0.1 m m stainless-steel wire; 0.5 mm tip separation) were implanted bilaterally into the L H A (A, 4 . 4 - 5 . 7 ; L, 1.5; H , - 3 . 2 ; n = 10) (ref. 8), and the cortex (A and L, the same as L H A ; H, 1.0 mm down from the cortex surface; n = 5). One week after surgery, the animal was artificially respired and anesthetized with 1.0% halothane in 0 2 A d r e n a l venous blood samples were collected through a Y-shaped polyethylene catheter inserted into the left adrenal vein via the left renal vein. W h e n samples were not being collected, the adrenal venous blood was shunted into the right femoral vein. Blood pressure was monitored continuously from the right common carotid artery. The details of methods have been previously described 1 The L H A was stimulated with rectangular current pulses (0.1 m A , 0.1 ms, 20, 50 and 100 Hz for 1 min) through the electrodes, and then lesions were made

Correspondence Y Oomura, Department of Physiology, Faculty of Med]cme, Kyushu Umverslty 60, Fukuoka 812, Japan 0006-8993/86/$03 50 (~) 1986 Elsevier Science Pubhshers B V (Biomedical Division)

142 by passing D C current (2 m A , for 15 s). A d r e n a l blood samples (50-100 bd) were taken 3 min before, during and 1 min after stimulation at each frequency In lesion experiments, they were taken 15 and 2 min before, and 2, 15, 30, 45 and 60 min after lesion. The contents of epinephrine (E) and n o r e p i n e p h r i n e (NE) were m e a s u r e d using high-performance liquid chromatography. The secretion rate was calculated from the absolute C A concentration and the adrenal plasma flowrate t. Following the completion of experiments, the lesion loci were verified histologically. The control (prestimulation) secretion rate of adrenal C A s varied from rat to rat but was stable before stimulation and lesion in a given animal. M e a n values of secretion rate were as follows; E, 36.6 + 6.1 ng/kg/mm (mean + S . E . M . , range 12.8-79.9 ng/kg/min, n = 10) and N E , 9.2 + 1.7 ng/kg/mm (range 2.9-15.8 ng/kg/mm). No response of C A secretion was observed at 20 Hz stimulation in any group. L H A - s t i m u l a t i o n sites could be classified into

3 groups ( A , B and C) on the basis of the occurrence and direction of the change in secretion rate of E e v o k e d during stimulation at 50 Hz. The criterion for a change in secretion rate was defined as 10% above or below the control level. A s shown in Fig. 1, group A (n = 4) d e m o n s t r a t e d an increased E secretion rate on L H A stimulation at 50 Hz and a larger response at 100 Hz. This group showed no change m N E secretion rate at any frequency. G r o u p B (n = 3) showed decreased E secretion rate on stimulation at 50 and 100 Hz, and decreased N E secretion rate at 100 Hz. G r o u p C (n = 3) showed no change in E secretion rate at any frequency, but decreased N E secretion rate at 100 Hz. This selective secretion of E and N E has been also observed in cats3, t0 E secretion rates of all 3 groups decreased significantly during the first 15-min interval following the L H A lesion, while cortical lesions, which served as controls, caused no significant change in both E and N E secretion rates (Fig. 2). The most suppressive re-

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Fig 1 Responses of E (upper) and NE (lower) secretion rates from adrenal medulla to LHA stzmulauon (0 1 mA, 0 1 ms, i mm) Percent change from control level Vertical bar at each point = standard error O----Q, group A (n = 4); A - - A , group B (n = 3); ~ , group C (n = 3) No responses were observed at 20 Hz stlmulauon in all groups * P < 0 05. ** P < 0 01, paired sample t-test after angular transformation

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Fig. 2. Responsesof E (upper) and NE (lower) secretion rates from adrenal medulla to LHA lesion (2 mA, DC, 15 s). O--Q, group A; & - - & , group B; O--O, group C; (1'-.-.--O, effect of cortical lesion. * P < 0 05, ** P < 0.01, t-test.

sponse was observed in group A, with a smaller decrease in E secretion occurring in group C and less still observed in group B. NE secretion also showed a maximal decrease after lesions in group A (Fig. 2, lower). The NE secretion rate of group C showed a smaller but still significant decrease after lesion, and an even smaller effect was observed in group B, although it was not significant. The short duration (15 min) of the lesion effect on CA secretion was not expected. This can be due to the partial destruction of the L H A and compensatory mechanisms occurring in the remaining tissue. Effects of L H A stimulation at 50 Hz on systolic blood pressure (BP) indicated that group A showed the most pressor effects (14.0 + 3.6 mm Hg, mean change + S.D.), except for one case which showed no change in BP at all. The responses of BP appeared within a few seconds and persisted during stimulation. Group B also showed a mild pressor response (5.3 + 0.6 mm Hg), and group C no significant change (-1.0 + 4.9 mm Hg). In lesion experiment, 8

out of 10 cases showed a decrease in BP (-18.9 + 6.2 mm Hg) within at least 15 min, which continued for 60 min. The remaining two cases showed no significant change in BP. Since an increase in BP was observed in group B as well as group A, the L H A might have a pathway for activation of the cardiovascular system that is different from the one for adrenal activation. The results indicated that the effect of stimulation on CA secretion was not the opposite of that of lesioning. However, the acute lesion made by passing a DC current may cause irritation around the site of destruction, and result in a stimulatory effect. Lesion of the sites at which stimulation showed no change in the E secretion rate (group C), as well as those showing increase in E secretion rate (group A), caused decrease in E secretion (Fig. 2, upper). Thus, it is likely that the effects of lesions result from a loss of influence of these sites on E secretion. In addition, if so, the lesion study suggests that the L H A has predominantly a facilitatory influence on E secretion from the adrenal medulla. There was no specific relationship between the sites of stimulation and the direction of response, as shown in Fig. 3. The present results indicated both increased and decreased CA secretion rates from the adrenal mestimulation

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Fig. 3. Histological map (according to ref. 8) depleting effects of stlmulaUons (left) and lesions (right) at the same LHA sites. Q, Increase; A, decrease; O, no change, in E secretion rate from adrenal medulla. LHA, lateral hypothalamie area; VMH, ventromedlal hypothalarmc nucleus; OT, optic tract.

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Education, Science and Culture, Japan

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for

This w o r k was s u p p o r t e d by Scientific

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