Brain Research, 543 (1991) 157-159 ADONIS 000689939124562V
157
BRES 24562
The activity of catecholamine synthesis in the hypothalamus of female normotensive Wistar Kyoto and spontaneously hypertensive rats Jun Arita, Ryuhei Hashimoto and Fukuko Kimura Department of Physiology, Yokohama City University School of Medicine, Yokohama (Japan) (Accepted 4 December 1990) Key words: Spontaneouslyhypertensive rat; Normotensive Wistar Kyoto rat; Catecholamine synthesis; Tuberoinfundibular dopaminergic neuron
The activity of catecholamine synthesis in the hypothalamus, as determined by the rate of 3,4-dihydroxyphenylalanine(DOPA) accumulation after the administration of a DOPA decarboxylase inhibitor, was compared among Wistar, spontaneously hypertensive (SH), and genetically matched normotensive Wistar Kyoto (WKY) rats. DOPA accumulation in the median eminence, an index of the activityof tuberoinfundibular dopaminergic neurons, was greater in SH rats than Wistar and WKY rats while DOPA accumulation in the medial preoptic area was smaller in Wistar rats than SH and WKY rats. No strain difference was found in DOPA accumulation in the corpus striatum, which represents the activity of nigrostriatal dopaminergic neurons. These results suggest that there are differences in catecholamine synthesis in the hypothalamus not only between SH and WKY rats but also between WKY and Wistar rats. Spontaneously hypertensive (SH) rats have many differences in a variety of body functions including endocrine function in comparison with genetically matched normotensive Wistar Kyoto (WKY) rats 17. However, McMurtry and Wexler 14'24 have argued against the appropriateness of the WKY rat as a counter model to the SH rat on the basis of the rejection rate of transplantation of the pituitary and adrenal glands. In fact, we have recently shown that there are differences in the pulsatile patterns of luteinizing hormone (LH) and prolactin secretion and the effects of immobilization stress on these patterns not only between ovariectomized SH and WKY rats but also between these rats and ordinary Wistar rats 9. These findings indicate the possibility that the neuronal function of the hypothalamus, which controls the secretion of LH and prolactin from the anterior pituitary, differs between these strains. Since catecholamine in the hypothalamus is known to be involved in the control of LH and prolactin secretion 23, the activities of catecholamine synthesis in the median eminence (ME) and medial preoptic area (MPO) of ovariectomized SH, WKY and Wistar rats were compared in the present study. Eight-week-old female SH, WKY and ordinary Wistar rats were purchased from Charles River Japan, Inc. They were ovariectomized under ether anesthesia. Systolic blood pressures, as measured by an indirect tail cuff
method using the rat-tail manometer system, in SH, WKY and Wistar rats were 199 + 3 (n = 10), 143 + 7 (n = 7) and 123 + 6 (n = 10) mmHg, respectively. The synthesis of catecholamine in the hypothalamus and corpus striatum (CS) was estimated by in vivo 3,4-dihydroxyphenylalanine (DOPA) accumulation5. The animals were injected ip with 100 mg/kg 3-hydroxybenzylhydrazine (NSD 1015) and decapitated after 45 rain. After the brain was quickly removed, a coronal forebrain slice for dissecting the MPO and CS and a sagittal hypothalamic slice for dissecting the ME were prepared using a sharp razor blade. Then, the tissues of the MPO and CS were bilaterally and unilaterally, respectively, punched out of the coronal slice with a stainless steel cannula (i.d. 0.7 mm). The tissue of the ME was dissected from the sagittal slice with the aid of a dissecting microscope and fine scissors 2. The tissue dissected was homogenized in 100/A 0.1 N perchloric acid containing 3 mM EDTA and 5 mM sodium metabisulfite. D O P A was determined with HPLC equipped with electrochemical detection, as described previously2. Values are expressed as ng of D O P A accumulated per mg protein per h. Differences between groups were analyzed by one-way analysis of variance followed by Duncan's multiple range test 7. D O P A accumulation in the ME was 17.4 + 2.0 (mean __ S.E.M., n = 10) ng per mg protein per h in Wistar rats.
Correspondence: J. Arita, Department of Physiology,YokohamaCity University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236, Japan.
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suggesting that a central dopaminergic insufficiency is involved in the d e v e l o p m e n t and maintenance of hypertension in SH rats 4"1°'15'16. D O P A accumulation in the M E after N S D 1015 injection is a reliable index for the
synthesis of d o p a m i n e in tuberoinfundibular dopaminergic ( T I D A ) neurons 6. The result that D O P A accumulation in the M E of SH rats was greater than that in W K Y and Wistar rats suggests that d o p a m i n e synthesis in T I D A neurons is stimulated in SH rats. This is in contrast to the finding r e p o r t e d by Steger et al. 2] that there was no difference in D O P A accumulation in the M E between ovariectomized SH and W K Y rats. A t present, we have no explanation for the inconsistency between their and our results. Since d o p a m i n e synthesized and released in T I D A neurons serves as a prolactin release inhibiting factor 3, the difference in d o p a m i n e synthesis in T I D A neurons between SH rats and the o t h e r two strains seemed reponsible for that in prolactin secretion between them as r e p o r t e d previously 9. H o w e v e r , we have previously shown that the overall m e a n of prolactin concentrations was rather greater in SH rats than Wistar rats and that the overall mean was not different between SH and W K Y rats. Based on the fact of no inverse relationship between d o p a m i n e synthesis in T I D A neurons and prolactin secretion in the three strains, it would be better to consider that the change in prolactin secretion in SH rats is not due to the change in the function of T I D A neurons but due to the change in the function of nondopaminergic neurons, e.g. prolactin releasing factor producing neurons, such as vasoactive intestinal p e p t i d e neurons 1'11"19 and oxytocin neurons 8"~3'2°. On the other hand, D O P A accumulation in the M P O after NSD 1015 injection reveals the synthetic activity of both d o p a m i n e and n o r e p i n e p h r i n e terminals in the M P O . The increased synthetic activity in the M P O of W K Y and SH rats may be related to a greater overall mean of L H concentrations in W K Y and SH rats than that in Wistar rats 9. The result in the present study that D O P A accumulation in the M P O of W K Y rats was significantly greater than that of Wistar rats indicates that there is a difference in the neuronal function even b e t w e e n W K Y and Wistar rats. Thus, it is a p p r o p r i a t e to use ordinary Wistar rats as well as W K Y rats as the control when functional differences in SH rats are investigated.
1 Abe, H., Engler, D., Molitch, M.E., Bollinger-Gruber, J. and Reichlin, S., Vasoactive intestinal peptide is a physiological mediator of prolactin release in the rat, Endocrinology, 116 (1985) 1383-1390. 2 Arita, J. and Kimura, E, Estimation of in vitro activity of tuberoinfundibular dopaminergic neurons by measurement of DOPA synthesis in the median eminence of hypothalamic slices, Neuroendocrinology, 39 (1984) 524-529. 3 Ben-Jonathan, N,, Dopamine: a prolactin inhibiting hormone, Endocr. Rev., 6 (1985) 564-589. 4 Bhargava, H.N., Effect of cyclo (leu-gly) on the supersensitivity of dopamine receptors in spontaneously hypertensive rats, Life Sci., 32 (1983) 2131-2137.
5 Carlsson, A. and Lindqvist, M., In vivo measurement of tryptophan and tyrosine hydroxylase activities in mouse brain, J. Neural Transm., 34 (1973) 79-91. 6 Demarest, K.T. and Moore, K.E., Accumulation of 1-Dopa in the median eminence: an index of tuberoinfundibular dopaminergic nerve activity, Endocrinology, 106 (1980) 463-468. 7 Duncan, D.B., Multiple range and multiple F tests, Biometrics, 11 (1955) 1-25. 8 Gibbs, D.M., High concentrations of oxytocin in hypophysial portal plasma, Endocrinology, 114 (1984) 1216-1218. 9 Hashimoto, R., Arita, J. and Kimura, F., LH and PRL secretion in ovariectomized spontaneously hypertensive rats, Acta Endocrinol., 122 (1990) 540-544.
_ 25 /
~**--2q.
|
°i ~g
N
|
|
/
lO
OL-. Wk;twWKY SH
WletKWKY ~
WIo~rWKY SH
Fig. 1. DOPA accumulation in the median eminence (left), medial preoptic area (middle) and corpus striatum (right panel) of Wistar, Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats. Ovariectomized rats were injected i.p. with 100 mg/kg NSD 1015 45 min before decapitation. DOPA accumulated in each tissue was determined by HPLC and electrochemical detection. Each column and its vertical line represent the mean and S.E.M., respectively, based on 7-10 animals. *Significantly different at P < 0.01.
A l t h o u g h W K Y rats showed a similar value of D O P A accumulation, D O P A accumulation in the M E of SH rats was significantly greater than that of Wistar and W K Y rats ( P < 0.01) (Fig. 1, left panel). D O P A accumulation in the M P O was 2.5 + 0.3 (n = 10) ng p e r mg protein p e r h in Wistar rats. There was no significant difference in D O P A accumulation in the M P O between W K Y and SH rats (middle panel). H o w e v e r , D O P A accumulation was significantly greater in W K Y and SH rats than Wistar rats ( P < 0.01). On the o t h e r hand, there was no difference in D O P A accumulation in the CS among these three strains (right panel). It has been shown that the function of catecholaminergic neurons in the central nervous system is altered in SH rats 12A8'22'25. In particular, there is a line of evidence
159 10 Hutchinson, J.S., DiNicolantonio, R., Veroni, M. and Cleverdon, M., Evidence for a functional central dopaminergic insufficiency in the spontaneously hypertensive rat, Clin. Exp. Pharmacol. Physiol., 10 (1983) 311-314. 11 Kato, Y., Iwasaki, Y., Iwasaki, J., Abe, H., Yanaihara, N. and Imura, H., Prolactin release by vasoactive intestinal polypeptide in rats, Endocrinology, 103 (1978) 554-558. 12 Koulu, M., Saavedra, J.M., Niwa, M. and Linnoila, M., Increased catecholamine metabolism in the locus coeruleus of young spontaneously hypertensive rats, Brain Research, 369 (1986) 361-364. 13 Lumpkin, M.D., Samson, W.K. and McCann, S.M., Hypothalamic and pituitary sites of action of oxytocin to alter prolactin secretion in the rat, Endocrinology, 112 (1983) 1711-1717. 14 McMurtry, J.P. and Wexler, B.C., Hypersensitivity of spontaneously hypertensive rats (SHR) to heat, ether, and immobilization, Endocrinology, 108 (1981) 1730-1736. 15 Myers, M.M., Whittemore, S.R. and Hendley, E.D., Changes in catecholamine neuronal uptake and receptor binding in the brains of spontaneously hypertensive rats, Brain Research, 220 (1981) 325-338. 16 Nagahama, S., Chen, Y.-E and Oparil, S., Mechanism of the depressor effect of bromocriptine in the spontaneously hypertensive rat, J. Pharmacol. Exp. Ther., 228 (1984) 370-375. 17 Okamoto, K. , Spontaneous Hypertension: Its Pathogenesis and Complications, Igaku Shoin, Tokyo, 1972. 18 Saavedra, J.M., Grobecker, H. and Axelrod, J., Changes in
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central catecholaminergic neurons in the spontaneously (genetic) hypertensive rat, Circ. Res., 42 (1978) 529-534. Said, S.I. and Porter, J.C., Vasoactive intestinal polypeptide: release into hypophyseal portal blood, Life Sci., 24 (1979) 227-230. Samson, W.K., Lumpkin, M.D. and McCann, S.M., Evidence for a physiological role for oxytocin in the control of prolactin secretion, Endocrinology, 119 (1986) 554-560. Steger, R.W., Avila-Jimenez, R., Amador, A. and Johns, A., Altered hypothalamic monoamine metabolism and pituitary prolactin regulation in female spontaneously hypertensive rats, Life Sci. 34 (1984) 1691-1697. Versteeg, D.H.G., Palkovits, M., Van der Gugten, J., Wijnen, H.L.J.M., Smeets, G.W.M. and Jong, W. de, Catecholamine content of individual brain regions of spontaneously hypertensive rats (SH-rats), Brain Research, 112 (1976) 429-434. Weiner, R.I. and Ganong, W.F., Role of brain monoamines and histamine in regulation of anterior pituitary secretion, Physiol. Rev., 58 (1978) 905-976. Wexler, B.C., Transplantation of pituitary and adrenal glands of spontaneously hypertensive rats into hypophysectomized or adrenalectomized, normotensive Sprague-Dawley rats, Br. J. Exp. Pathol., 61 (1980) 429-439. Yamori, Y., Lovenberg, W. and Sjoerdsma, A., Norepinephrine metabolism in brainstem of spontaneously hypertensive rats, Science, 170 (1970) 544-546.
157
BRES 24562
The activity of catecholamine synthesis in the hypothalamus of female normotensive Wistar Kyoto and spontaneously hypertensive rats Jun Arita, Ryuhei Hashimoto and Fukuko Kimura Department of Physiology, Yokohama City University School of Medicine, Yokohama (Japan) (Accepted 4 December 1990) Key words: Spontaneouslyhypertensive rat; Normotensive Wistar Kyoto rat; Catecholamine synthesis; Tuberoinfundibular dopaminergic neuron
The activity of catecholamine synthesis in the hypothalamus, as determined by the rate of 3,4-dihydroxyphenylalanine(DOPA) accumulation after the administration of a DOPA decarboxylase inhibitor, was compared among Wistar, spontaneously hypertensive (SH), and genetically matched normotensive Wistar Kyoto (WKY) rats. DOPA accumulation in the median eminence, an index of the activityof tuberoinfundibular dopaminergic neurons, was greater in SH rats than Wistar and WKY rats while DOPA accumulation in the medial preoptic area was smaller in Wistar rats than SH and WKY rats. No strain difference was found in DOPA accumulation in the corpus striatum, which represents the activity of nigrostriatal dopaminergic neurons. These results suggest that there are differences in catecholamine synthesis in the hypothalamus not only between SH and WKY rats but also between WKY and Wistar rats. Spontaneously hypertensive (SH) rats have many differences in a variety of body functions including endocrine function in comparison with genetically matched normotensive Wistar Kyoto (WKY) rats 17. However, McMurtry and Wexler 14'24 have argued against the appropriateness of the WKY rat as a counter model to the SH rat on the basis of the rejection rate of transplantation of the pituitary and adrenal glands. In fact, we have recently shown that there are differences in the pulsatile patterns of luteinizing hormone (LH) and prolactin secretion and the effects of immobilization stress on these patterns not only between ovariectomized SH and WKY rats but also between these rats and ordinary Wistar rats 9. These findings indicate the possibility that the neuronal function of the hypothalamus, which controls the secretion of LH and prolactin from the anterior pituitary, differs between these strains. Since catecholamine in the hypothalamus is known to be involved in the control of LH and prolactin secretion 23, the activities of catecholamine synthesis in the median eminence (ME) and medial preoptic area (MPO) of ovariectomized SH, WKY and Wistar rats were compared in the present study. Eight-week-old female SH, WKY and ordinary Wistar rats were purchased from Charles River Japan, Inc. They were ovariectomized under ether anesthesia. Systolic blood pressures, as measured by an indirect tail cuff
method using the rat-tail manometer system, in SH, WKY and Wistar rats were 199 + 3 (n = 10), 143 + 7 (n = 7) and 123 + 6 (n = 10) mmHg, respectively. The synthesis of catecholamine in the hypothalamus and corpus striatum (CS) was estimated by in vivo 3,4-dihydroxyphenylalanine (DOPA) accumulation5. The animals were injected ip with 100 mg/kg 3-hydroxybenzylhydrazine (NSD 1015) and decapitated after 45 rain. After the brain was quickly removed, a coronal forebrain slice for dissecting the MPO and CS and a sagittal hypothalamic slice for dissecting the ME were prepared using a sharp razor blade. Then, the tissues of the MPO and CS were bilaterally and unilaterally, respectively, punched out of the coronal slice with a stainless steel cannula (i.d. 0.7 mm). The tissue of the ME was dissected from the sagittal slice with the aid of a dissecting microscope and fine scissors 2. The tissue dissected was homogenized in 100/A 0.1 N perchloric acid containing 3 mM EDTA and 5 mM sodium metabisulfite. D O P A was determined with HPLC equipped with electrochemical detection, as described previously2. Values are expressed as ng of D O P A accumulated per mg protein per h. Differences between groups were analyzed by one-way analysis of variance followed by Duncan's multiple range test 7. D O P A accumulation in the ME was 17.4 + 2.0 (mean __ S.E.M., n = 10) ng per mg protein per h in Wistar rats.
Correspondence: J. Arita, Department of Physiology,YokohamaCity University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236, Japan.
158
suggesting that a central dopaminergic insufficiency is involved in the d e v e l o p m e n t and maintenance of hypertension in SH rats 4"1°'15'16. D O P A accumulation in the M E after N S D 1015 injection is a reliable index for the
synthesis of d o p a m i n e in tuberoinfundibular dopaminergic ( T I D A ) neurons 6. The result that D O P A accumulation in the M E of SH rats was greater than that in W K Y and Wistar rats suggests that d o p a m i n e synthesis in T I D A neurons is stimulated in SH rats. This is in contrast to the finding r e p o r t e d by Steger et al. 2] that there was no difference in D O P A accumulation in the M E between ovariectomized SH and W K Y rats. A t present, we have no explanation for the inconsistency between their and our results. Since d o p a m i n e synthesized and released in T I D A neurons serves as a prolactin release inhibiting factor 3, the difference in d o p a m i n e synthesis in T I D A neurons between SH rats and the o t h e r two strains seemed reponsible for that in prolactin secretion between them as r e p o r t e d previously 9. H o w e v e r , we have previously shown that the overall m e a n of prolactin concentrations was rather greater in SH rats than Wistar rats and that the overall mean was not different between SH and W K Y rats. Based on the fact of no inverse relationship between d o p a m i n e synthesis in T I D A neurons and prolactin secretion in the three strains, it would be better to consider that the change in prolactin secretion in SH rats is not due to the change in the function of T I D A neurons but due to the change in the function of nondopaminergic neurons, e.g. prolactin releasing factor producing neurons, such as vasoactive intestinal p e p t i d e neurons 1'11"19 and oxytocin neurons 8"~3'2°. On the other hand, D O P A accumulation in the M P O after NSD 1015 injection reveals the synthetic activity of both d o p a m i n e and n o r e p i n e p h r i n e terminals in the M P O . The increased synthetic activity in the M P O of W K Y and SH rats may be related to a greater overall mean of L H concentrations in W K Y and SH rats than that in Wistar rats 9. The result in the present study that D O P A accumulation in the M P O of W K Y rats was significantly greater than that of Wistar rats indicates that there is a difference in the neuronal function even b e t w e e n W K Y and Wistar rats. Thus, it is a p p r o p r i a t e to use ordinary Wistar rats as well as W K Y rats as the control when functional differences in SH rats are investigated.
1 Abe, H., Engler, D., Molitch, M.E., Bollinger-Gruber, J. and Reichlin, S., Vasoactive intestinal peptide is a physiological mediator of prolactin release in the rat, Endocrinology, 116 (1985) 1383-1390. 2 Arita, J. and Kimura, E, Estimation of in vitro activity of tuberoinfundibular dopaminergic neurons by measurement of DOPA synthesis in the median eminence of hypothalamic slices, Neuroendocrinology, 39 (1984) 524-529. 3 Ben-Jonathan, N,, Dopamine: a prolactin inhibiting hormone, Endocr. Rev., 6 (1985) 564-589. 4 Bhargava, H.N., Effect of cyclo (leu-gly) on the supersensitivity of dopamine receptors in spontaneously hypertensive rats, Life Sci., 32 (1983) 2131-2137.
5 Carlsson, A. and Lindqvist, M., In vivo measurement of tryptophan and tyrosine hydroxylase activities in mouse brain, J. Neural Transm., 34 (1973) 79-91. 6 Demarest, K.T. and Moore, K.E., Accumulation of 1-Dopa in the median eminence: an index of tuberoinfundibular dopaminergic nerve activity, Endocrinology, 106 (1980) 463-468. 7 Duncan, D.B., Multiple range and multiple F tests, Biometrics, 11 (1955) 1-25. 8 Gibbs, D.M., High concentrations of oxytocin in hypophysial portal plasma, Endocrinology, 114 (1984) 1216-1218. 9 Hashimoto, R., Arita, J. and Kimura, F., LH and PRL secretion in ovariectomized spontaneously hypertensive rats, Acta Endocrinol., 122 (1990) 540-544.
_ 25 /
~**--2q.
|
°i ~g
N
|
|
/
lO
OL-. Wk;twWKY SH
WletKWKY ~
WIo~rWKY SH
Fig. 1. DOPA accumulation in the median eminence (left), medial preoptic area (middle) and corpus striatum (right panel) of Wistar, Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats. Ovariectomized rats were injected i.p. with 100 mg/kg NSD 1015 45 min before decapitation. DOPA accumulated in each tissue was determined by HPLC and electrochemical detection. Each column and its vertical line represent the mean and S.E.M., respectively, based on 7-10 animals. *Significantly different at P < 0.01.
A l t h o u g h W K Y rats showed a similar value of D O P A accumulation, D O P A accumulation in the M E of SH rats was significantly greater than that of Wistar and W K Y rats ( P < 0.01) (Fig. 1, left panel). D O P A accumulation in the M P O was 2.5 + 0.3 (n = 10) ng p e r mg protein p e r h in Wistar rats. There was no significant difference in D O P A accumulation in the M P O between W K Y and SH rats (middle panel). H o w e v e r , D O P A accumulation was significantly greater in W K Y and SH rats than Wistar rats ( P < 0.01). On the o t h e r hand, there was no difference in D O P A accumulation in the CS among these three strains (right panel). It has been shown that the function of catecholaminergic neurons in the central nervous system is altered in SH rats 12A8'22'25. In particular, there is a line of evidence
159 10 Hutchinson, J.S., DiNicolantonio, R., Veroni, M. and Cleverdon, M., Evidence for a functional central dopaminergic insufficiency in the spontaneously hypertensive rat, Clin. Exp. Pharmacol. Physiol., 10 (1983) 311-314. 11 Kato, Y., Iwasaki, Y., Iwasaki, J., Abe, H., Yanaihara, N. and Imura, H., Prolactin release by vasoactive intestinal polypeptide in rats, Endocrinology, 103 (1978) 554-558. 12 Koulu, M., Saavedra, J.M., Niwa, M. and Linnoila, M., Increased catecholamine metabolism in the locus coeruleus of young spontaneously hypertensive rats, Brain Research, 369 (1986) 361-364. 13 Lumpkin, M.D., Samson, W.K. and McCann, S.M., Hypothalamic and pituitary sites of action of oxytocin to alter prolactin secretion in the rat, Endocrinology, 112 (1983) 1711-1717. 14 McMurtry, J.P. and Wexler, B.C., Hypersensitivity of spontaneously hypertensive rats (SHR) to heat, ether, and immobilization, Endocrinology, 108 (1981) 1730-1736. 15 Myers, M.M., Whittemore, S.R. and Hendley, E.D., Changes in catecholamine neuronal uptake and receptor binding in the brains of spontaneously hypertensive rats, Brain Research, 220 (1981) 325-338. 16 Nagahama, S., Chen, Y.-E and Oparil, S., Mechanism of the depressor effect of bromocriptine in the spontaneously hypertensive rat, J. Pharmacol. Exp. Ther., 228 (1984) 370-375. 17 Okamoto, K. , Spontaneous Hypertension: Its Pathogenesis and Complications, Igaku Shoin, Tokyo, 1972. 18 Saavedra, J.M., Grobecker, H. and Axelrod, J., Changes in
19 20 21
22
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25
central catecholaminergic neurons in the spontaneously (genetic) hypertensive rat, Circ. Res., 42 (1978) 529-534. Said, S.I. and Porter, J.C., Vasoactive intestinal polypeptide: release into hypophyseal portal blood, Life Sci., 24 (1979) 227-230. Samson, W.K., Lumpkin, M.D. and McCann, S.M., Evidence for a physiological role for oxytocin in the control of prolactin secretion, Endocrinology, 119 (1986) 554-560. Steger, R.W., Avila-Jimenez, R., Amador, A. and Johns, A., Altered hypothalamic monoamine metabolism and pituitary prolactin regulation in female spontaneously hypertensive rats, Life Sci. 34 (1984) 1691-1697. Versteeg, D.H.G., Palkovits, M., Van der Gugten, J., Wijnen, H.L.J.M., Smeets, G.W.M. and Jong, W. de, Catecholamine content of individual brain regions of spontaneously hypertensive rats (SH-rats), Brain Research, 112 (1976) 429-434. Weiner, R.I. and Ganong, W.F., Role of brain monoamines and histamine in regulation of anterior pituitary secretion, Physiol. Rev., 58 (1978) 905-976. Wexler, B.C., Transplantation of pituitary and adrenal glands of spontaneously hypertensive rats into hypophysectomized or adrenalectomized, normotensive Sprague-Dawley rats, Br. J. Exp. Pathol., 61 (1980) 429-439. Yamori, Y., Lovenberg, W. and Sjoerdsma, A., Norepinephrine metabolism in brainstem of spontaneously hypertensive rats, Science, 170 (1970) 544-546.
