Down-regulation of alpha 2 adrenoceptors in ventrolateral medulla of spontaneously hypertensive rats.

The binding of [3H]idazoxan [correction of idaxazon] to imidazole sites and [3H]rauwolscine to alpha 2 adrenoceptors of neuronal membranes prepared from cerebral cortex and ventrolateral medulla of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. [3H]idazoxan [correction of idaxazon] bound to the membranes of cerebral cortex and ventrolateral medulla at a single high affinity site. The binding of [3H]idazoxan [correction of idaxazon] in ventrolateral medulla and cerebral cortex was found to be similar in SHR and WKY rats. [3H]Rauwolscine bound to the membranes of cerebral cortex and ventrolateral medulla at a single high affinity site. The binding of [3H]rauwolscine in the cerebral cortex was found to be similar in SHR and WKY rats. However, in the ventrolateral medulla [3H]rauwolscine binding was found to be significantly lower in SHR as compared to WKY rats. The decreased binding was due a decrease (32%) in the Bmax value in SHR rats as compared to WKY rats. The Kd values were similar in SHR and WKY rats. It is concluded that imidazole binding sites are not affected while, alpha 2 adrenergic binding sites are decreased in the ventrolateral medulla of SHR rats and may be contributing to the regulation of blood pressure.     

Autoradiographic Localization of [125I-Tyr0]Bradykinin Binding Sites in Brains of Wistar-Kyoto and Spontaneously Hypertensive Rats

1. The present study was undertaken to localize and characterize bradykinin (BK) binding sites in brains from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR).2. Serial sections of brains were cut from adult WKY and SHR and specific [¹²⁵I-Tyr⁰]bradykinin ([¹²⁵I-Tyr⁰]BK) binding was determined using in vitro quantitative receptor autoradiographic techniques.3. Specific binding of [¹²⁵I Tyr⁰]BK was localized in the medulla oblongata to the regions of the nucleus of the solitary tract (NTS), area postrema (AP), dorsal motor nucleus of the vagus (X), and caudal subnucleus of the spinal trigeminal nucleus in both strains of rat. The specific binding (85–90% of total binding) was of high affinity and saturable with K _D values in the range of 100 pM and a B _max of 0.75 fmol per mg tissue equivalent in the NTS–X–AP complex of both the WKY and SHR. In competition studies, the rank order of potencies was similar in both strains with BK = Lys-BK > icatibant >>> DesArg⁹-BK. The B₂ receptor antagonist icatibant inhibited [¹²⁵I-Tyr⁰]BK binding with a K _i value of 0.63 ± 0.19 nM in WKY and 0.91 ± 0.73 nM in SHR, while K _i values for the B> ₁ receptor agonist DesArg⁹-BK were 1475 ± 1055 and 806 ± 362 nM in WKY and SHR, respectively.4. Our finding of specific high-affinity [¹²⁵I-Tyr⁰]BK B₂ binding sites in the NTS, AP, and the X of WKY and SHR is important because these brain areas are associated with central cardiovascular regulation. However, alterations in BK B₂ receptors in the medulla that could contribute to the hypertensive state in the SHR were not detected.     

Presynaptic Modulation of K+-Evoked [3H]Dopamine Release in Striatal and Frontal Cortical Synaptosomes of Normotensive and Spontaneous-Hypertensive Rats

Regional differences in presynaptic [³H]dopamine ([³H]DA) release and its modulation by D₂ DA-receptors between the frontal cortex and striatum obtained from Wystar-Kyoto (WKY) and spontaneous-hypertensive rats (SHR) have been evaluated using superfused synaptosomes. Synaptosomal tritium content was significantly lower in the frontal cortex than in the striatum in both SHR and WKY (45% and 48%, respectively), but no differences in tritium content were obtained between strains. However, the 15 mM K⁺-evoked [³H]DA overflow was lower in the SHR as compared to WKY rats in both brain regions (striatum 23%, frontal cortex 21). Concentration-response curves for quinpirole (1nM-10 M)-mediated inhibition of 15mM K⁺-evoked [³H]DA release showed no differences between SHR and WKY. These results suggest that SHR has less ability to release [³H]DA as compared to WKY rats, but SHR did not show differences in the autoregulation of such release in both the frontal cortex and striatum.     

Proliferation of thyrotropin releasing hormone receptors in specific brain regions during the development of hypertension in spontaneously hypertensive rats

The binding of [3H] [3-MeHis2] thyrotropin releasing hormone [( 3H]MeTRH) to brain membranes prepared from 8 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. [3H]MeTRH bound specifically to rat brain membranes at a single high affinity site. The density (Bmax value) of [3H]MeTRH binding sites was significantly greater (28%) in SHR rats compared to WKY rats. The apparent dissociation constants (Kd values) for the binding of [3H]MeTRH in SHR and WKY rats did not differ. Binding in the various brain regions revealed that the density of [3H]MeTRH was highest in the hypothalamus followed in decreasing order by pons + medulla, midbrain, cortex and striatum. The binding of [3H]MeTRH was approximately 25% greater in cortex, hypothalamus and striatum of SHR rats in comparison to WKY rats. The binding in pons + medulla, midbrain and pituitary of SHR and WKY rats did not differ. To assess the significance of increased binding sites for [3H]MeTRH in some brain regions of SHR rats, the binding studies were carried out during normotensive and hypertensive stages of postnatal age in the two strains. In 3 and 4 week old SHR rats there was neither an increase in blood pressure nor any increase in [3H]MeTRH binding in the hypothalamus and striatum as compared to age matched WKY rats. With the development of elevated blood pressure at 6 weeks, an increase in [3H]MeTRH binding in the hypothalamus and striatum of SHR rats in comparison to the tissues from WKY rats was observed. The results provide, for the first time, evidence for a parallel increase in the density of brain TRH receptors with elevation of blood pressure, and suggest that brain TRH receptors may play an important role in the pathophysiology of hypertension.     

On the role of NMDA receptors in blood pressure regulation in spontaneously hypertensive rats (SHR)

Summary In the present study the binding of [³H]MK-801 to glutamatergic receptors of the NMDA type was compared in spontaneously hypertensive (SHR) and normotensive (WKY) rats in various brain structures (including nucleus tractus solitarii) by quantitative receptor autoradiography. Additionally, blood pressure changes after treatment with the NMDA antagonist MK-801 were studied in both strains. There were no differences between SHR and WKY rats either in the level of [³H]MK-801 binding or in the hypertensive reaction to MK-801.     

Down-regulation of endothelin receptors in the ventrolateral medulla of spontaneously hypertensive rats.

The binding of [125I] sarafotoxin 6b (SRT 6b) and [125I] endothelin-1 (ET-1) to endothelin (ET) receptors of neuronal membranes prepared from cerebral cortex and ventrolateral medulla of 8 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. [125I] SRT 6b bound to the membranes of cerebral cortex and ventrolateral medulla at a single high affinity site. The binding of [125I] SRT 6b in the cerebral cortex was found to be similar in SHR and WKY rats. However, in the ventrolateral medulla [125I] SRT 6b binding was found to be significantly lower in SHR as compared to WKY rats. The decreased binding was due to decrease (48%) in the Bmax values in SHR rats as compared to WKY rats. The Kd values were similar in SHR and WKY rats. [125I] ET-1 also bound to the membranes of cerebral cortex and ventrolateral medulla at a single high affinity site. The binding of [125I] ET-1 in the cerebral cortex was found to be similar in SHR and WKY rats. However, in the ventrolateral medulla [125I] ET-1 binding was found to be significantly lower in SHR as compared to WKY rats. The decreased binding was due to 36% decrease in the Bmax values in SHR rats as compared to WKY rats. The Kd values were similar in SHR and WKY rats. It is concluded that the population of ET receptors is less in the ventrolateral medulla of SHR rats and may be contributing to the regulation of blood pressure.     

Some disturbances in the function of ryanodine receptors of spontaneously hypertensive rat cardiomyocytes detected using 4-chloro<Emphasis Type="Italic">m</Emphasis>-cresol

The rate of Ca²⁺ release from the sarcoplasmic reticulum in response to the activation of ryanodine receptors with 4-chlorom-cresol in the cardiomyocytes of three rat strains—spontaneously hypertensive (SHR), normotensive (WKY), and Wistar rats—during 5 weeks of their growth and development was studied aiming to detect the functional differences in the operation of these receptors at various stages of arterial hypertension. In response to 4-chlorom-cresol, a drastic increase in the rates of [Ca²⁺]_i accumulation in SHR myocytes after 17 days of development is recorded versus a decrease in the rates of Ca²⁺ efflux from the sarcoplasmic reticulum of Wistar and WKY rat cardiomyocytes. A correlation between this phenomenon and a genetic defect of ryanodine receptors in SHR rats seems rather unlikely, as the newborn WKY and SHR rats exposed to 4-chlorom-cresol at a concentration range of 0.5–2.0 mM did not display any differences in the rate of sarcoplasmic reticulum Ca²⁺ release. On the other hand, it is possible that the pathological changes in the function of ryanodine receptors manifest themselves later in the ontogenesis. The connection of this phenomenon with an increase in the role of ryanodine receptors in the excitation-contraction coupling in muscle cells and an increase in the calpain expression in SHR rats (absent in the WKY rats) by the age of 3 weeks is discussed. It is assumed that the cleavage of ryanodine receptor subunits by calpain can noticeably intensify the sarcoplasmic reticulum Ca²⁺ release after activation of these receptors without influencing the receptor binding characteristics.     

Competition by Estrogens for Catecholamine Receptor Binding In Vitro

Abstract: We have examined the ability of various steroids to compete for high-affinity binding of ³H-labeled ligands to catecholamine receptors in membranes prepared from rat cerebral cortex, striatum, and anterior pituitary. Ligands employed were: [³H]WB4101, [³H]prazosin, [³H]yohimbine, and [³H]clonidine (alpha-noradrenergic); [³H]dihydroalprenolol (beta-noradrenergic); [³H]spiperone and [³H]ADTN (dopaminergic). Only the 17β estrogens were effective and only binding of [³H]spiperone and [³H]ADTN in striatum and [³H]WB4101 and [³H]prazosin in cerebral cortex was reduced. Thus putative dopaminergic and alpha₁-noradrenergic sites alone appear to recognize estrogens. A slight competitive effect on [³H]spiperone binding to anterior pituitary membranes was also observed. Among the 17β estrogens tested, the most effective in all cases was the catechol estrogen 2-hydroxyestradiol (2-OHE₂). The ability of 2-OHE₂ (IC₅₀= 20–30 μM) to inhibit ligand binding to alpha₁ receptors was comparable to that of norepinephrine (IC₅₀= 10–20 μM), whereas for dopamine receptors in striatum and pituitary 2-OHE₂ was an order of magnitude less effective than dopamine (IC₃₀= 12 μM) in reducing binding of ³H ligands. Estradiol-17β and 2-hydroxyestrone were also able to inhibit binding, but the order of steroid potency was different for alpha₁ and dopaminergic receptors. Progesterone, testosterone, and corticosterone were without effect in all cases. These results show that there is specificity of steroid interactions with catecholamine receptors in the brain, both in terms of steroid structure and receptor type. The possible relevance of these interactions to neuroendocrine function is discussed.     

Up-regulation of serotonergic binding sites labeled by [3H]WB4101 following fimbrial transection and 5,7-dihydroxytryptamine-induced lesions

Lesions of the serotonergic afferents to the hippocampus, by fimbrial transection or by 5,7-dihydroxytryptamine treatment, produce an increase in the Bmax of [3H]WB4101 to its nanomolar affinity binding site, with no effect on its picomolar affinity binding site or on [3H]prazosin binding. The nanomolar site is serotonergic as the serotonergic agonists, serotonin and 8-hydroxydipropylaminotetraline (8-OH-DPAT) have nanomolar affinity for [3H]WB4101 binding when studied in the presence of a prazosin mask (30 nM) of the alpha-1 component of [3H]WB4101 binding. The serotonin receptor antagonists metergoline, lysergic acid diethylamide and lisuride also have high nanomolar affinities while ketanserin, yohimbine, prazosin and noradrenergic agonists have affinities in the micromolar range. Fimbrial transection or 5,7-dihydroxytryptamine injections produced 32% and 44% increases in the Bmax of [3H]WB4101 binding in the presence of a prazosin mask. Serotonin competition for [3H]WB4101 binding was identical in control and experimental tissue from each lesion experiment. Although specific binding of [3H]WB4101 was increased, there was no change in the affinities or the percentages of the two binding components for serotonin competition with [3H]WB4101. These data suggest that removal of the serotonergic input to the hippocampus produces an increase in the Bmax of serotonin receptor binding sites labeled by [3H]WB4101.     

Modulation of alpha-1 adrenergic receptors in rat brain following chronic reserpine

Functional denervation of the central adrenergic receptors by 30 daily injections of reserpine (0.25 mg/kg/day s.c.) produced an increase in the B_max of alpha-l adrenergic receptor binding sites labeled by [³H]prazosin. A similar increase was also observed for the alpha-1 adrenergic receptor component of [³H]WB4101 binding in the hippocampus but not in the cortex. No change in the lower affinity [³H]WB4101 binding site, which identifies S-l serotonin receptors was detected after this treatment. These data support the hypothesis that alpha-1 receptors are regulated by their neurotransmitter and may explain why previous studies have not detected alpha-1 receptor increases following 6-hydroxydopamine lesions of the dorsal bundle and locus coeruleus.     

Repeated Idazoxan Increases Brain Imidazoline Receptors in Normotensive (WKY) but Not in Hypertensive (SHR) Rats

The specific binding of [3H]idazoxan in the presence of 10(-6) M (-)-adrenaline was used to evaluate the density of imidazoline receptors in the brain of spontaneously hypertensive (SHR) rats and sex- and age-matched normotensive Wistar-Kyoto (WKY) rats. In SHR rats the density of imidazoline receptors (cerebral cortex, hypothalamus, and medulla oblongata) was not different from that in normotensive (WKY) rats. However, repeated treatment with idazoxan consistently increased (23-80%) the density of imidazoline receptors in the various brain regions of WKY rats but not in SHR rats. In normotensive Sprague-Dawley rats, repeated treatment with the imidazoline drugs idazoxan and cirazoline also increased (33-37%) the density of imidazoline receptors in the cerebral cortex. The lack of regulation by idazoxan of the density of imidazoline receptors in the brain of SHR rats might reflect the existence of a relevant abnormality of these receptors in this genetic model of hypertension.     

Characteristics of central binding sites for [3H] DAMGO in spontaneously hypertensive rats

The binding of [3H] DAMGO, a highly selective ligand for mu-opiate receptors, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. [3H] DAMGO bound to membranes of brain regions and spinal cord at a single high affinity site. The receptor density (Bmax value) and apparent dissociation constant (Kd value) of [3H] DAMGO to bind to membranes of hippocampus, corpus striatum, pons and medulla, cortex and spinal cord of WKY and SHR rats did not differ. The Bmax value of [3H] DAMGO in membranes of hypothalamus and midbrain of SHR rats was significantly higher than in WKY rats but the Kd values in the two strains did not differ. On the other hand, the Bmax value of [3H] DAMGO in membranes of amygdala of SHR rats was lower than that of WKY rats but the Kd values in the two strains were similar. It is concluded that SHR rats have higher density of mu-opiate receptors in hypothalamus and midbrain but lower density in amygdala in comparison with WKY rats, and that such differences in the distribution of mu-opiate receptors may be related to the elevated blood pressure in SHR rats.     

Biochemical Characterization of α-Adrenergic Receptors in Human Brain and Changes in Alzheimer-Type Dementia

Abstract Using ligand binding techniques, we studied α-adrenergic receptors in brains obtained at autopsy from seven histologically normal controls and seven patients with histopathologically verified Alzheimer-type dementia (ATD). Binding of the α-adrenergic antagonists [³H]prazosin and [³H]yohimbine to membranes of human brains exhibited characteristics compatible with α₁- and α₂-adrenergic receptors, respectively. Binding of both ligands was saturable and reversible, with dissociation constants of 0.15 nM for [³H]prazosin and 5.5 nM for [³H]yohimbine. [³H]Prazosin binding was highest in the hippocampus and frontal cortex and lowest in the caudate and putamen in the control brains. [³H]Yohimbine binding was highest in the nucleus basalis of Meynert (NbM) and frontal cortex and lowest in the caudate and cerebellar hemisphere in the control brains. Compared with values for the controls, [³H]prazosin binding sites were significantly reduced in number in the hippocampus and cerebellar hemisphere, and [³H]yohimbine binding sites were significantly reduced in number in the NbM in the ATD brains. These results suggest that α₁ and α₂-adrenergic receptors are present in the human brain and that there are significant changes in numbers of both receptors in selected regions in patients with ATD.     

Lipid composition and fluidity in the jejunal brush-border membrane of spontaneously hypertensive rats. Effects on activities of membrane-bound proteins

The lipid composition and fluidity of jejunal brush-border membrane vesicles (BBMV) have been studied in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats. The activities of both Na⁺-dependent D-glucose cotransport and Na⁺-H⁺ antiport have also been determined. A significant increase in the level of free cholesterol was observed in jejunal BBMV from SHR compared to WKY rats. Since phospholipid values did not change in either group of animals, a significant enhancement in the free cholesterol/phospholipid ratio was observed in SHR. A decrease in the levels of phosphatidylethanolamine together with an increase in the values of phosphatidylserine was observed in hypertensive rats. Although the content of phosphatidylcholine (PC) and sphingomyelin (SM) was not singificantly altered in SHR, the ratio PC/SM significantly increased in these animals when compared to WKY rats. The major fatty acids present in bursh-border membranes prepared from SHR and WKY rats were palmitic (160), stearic (180), oleic (181, n-9) and linoleic (182, n-6), and the fatty acid composition was not modified by the hypertension. A decreased fluorescence polarization, i.e., increased membrane fluidity, was observed in SHR, which was not correlated to the increased ratio of cholesterol/phospholipid found in the brush-border membrane isolated from these animals. These structural changes found in SHR were associated to an enhancement in both Na⁺-dependent D-glucose transport and Na⁺-H⁺ antiport activity in the jejunal BBMV of SHR.Abbreviations BBMV brush-border membrane vesicles - DPH 1,6-diphenyl-1,3,5-hexatriene - FC free cholesterol - PC phosphatidylcholine - PE phosphatidylethanolamine - PI phosphatidylinositol - PS phosphatidylserine - SM sphingomyelin - SHR spontaneously hypertensive rat - p steady-state fluoroscence polarization - r_s steady-state fluorescence anisotropy - WKY Wistar Kyoto     

Central neurotransmitter receptors in hypertensive rats

Muscarinic cholinergic ([³H]QNB), α₁ ? ([³H]WB-4101), and α₂ ? ([³H]clonidine) adrenergic ligand binding was measured in various regions of the brains of adult normotensive, spontaneously hypertensive, and DOCA-salt hypertensive rats. There was a 66% increase in the number of α₁-adrenergic receptors in hypothalamus of the spontaneously hypertensive rats as compared to normotensive controls, with no change in the K_d value. There were no other differences in the spontaneously hypertensive rats and none in the DOCA-salt model. α₁-Adrenergic binding was elevated in hypothalamus of spontaneously hypertensive rats 4–20 weeks of age even though blood pressure in the 4-week old animals was not at hypertensive levels (i.e., <150 mmHg). Treatment of adult spontaneously hypertensive rats with clonidine HCl significantly reduced blood pressure but failed to alter the binding of [³H]WB-4101 in hypothalamus. Thus, it appears that the enhanced number of α₁-adrenergic receptors in hypothalamus of spontaneously hypertensive rats is neither a consequence of the increased blood pressure, nor a phenomenon common to all models of hypertension.     

Glycine,Serine, and Leucine Metabolism in Different Regions of Rat Central Nervous System

We have investigated the glycine, serine and leucine metabolism in slices of various rat brain regions of 14-day-old or adult rats, using [1-¹⁴C]glycine, [2-¹⁴C]glycine, L-[3-¹⁴C]serine and L-[U-¹⁴C]leucine. We showed that the [1-¹⁴C]glycine oxidation to CO₂ in all regions studied occurs almost exclusively through its cleavage system (GCS) in brains of both 14-day-old and adults rats. In 14-day-old rats, the highest oxidation of [1-¹⁴C]glycine was in cerebellum and the lowest in medulla oblongata. In these animals, the L-[U-¹⁴C]leucine oxidation was lower than the [1-¹⁴C]glycine oxidation, except in medulla oblongata where both oxidations were the same. Serine was the amino acid that showed lowest oxidation to CO₂ in all structure studied. In adult rats brains, the highest oxidation of [1-¹⁴C]glycine was in cerebral cortex and the lowest in medulla oblongata. We have not seen difference in the lipid synthesis from both glycine labeled, neither in 14-day-old rats nor in adult ones, indicating that the lipids formed from glycine were not neutral. Lipid synthesis from serine was significantly high than lipid synthesis and from all other amino acids studied in all studied structures. Protein synthesis from L-[U-¹⁴C]leucine was significantly higher than that from glycine in all regions and ages studied.     

Electroconvulsive Shock Increases α1b-but Not α1a-Adrenoceptor Binding Sites in Rat Cerebral Cortex

Repeated administration of electroconvulsive shock (ECS) increases [3H]prazosin binding to alpha 1-adrenoceptors in rat cerebral cortex. In contrast, [3H]WB4101 binding in cortex has been reported to be unchanged after ECS. [3H]Prazosin labels two alpha 1-adrenoceptor subtypes, termed alpha 1a and alpha 1b, whereas [3H]WB4101 labels the alpha 1a subtype preferentially. The purpose of this study was to determine whether ECS increases one or both alpha 1-adrenoceptor subtypes in rat cerebral cortex. We found that treatment of rats with ECS once daily for 10-12 days increased [3H]prazosin binding in cortex by about 25% but did not significantly alter [3H]WB4101 binding to alpha 1-adrenoceptors. Measurement of alpha 1a and alpha 1b receptors by competition analysis of the selective alpha 1a antagonist 5-methylurapidil against [3H]prazosin and measurement of [3H]prazosin binding in homogenates preincubated with chlorethylclonidine, which alkylates alpha 1b binding sites, also indicated that the ECS-induced increase in alpha 1-adrenoceptors is confined to the alpha 1b subtype. In contrast to its effect on [3H]prazosin binding, ECS did not increase phosphoinositide hydrolysis as measured by [3H]inositol 1-phosphate accumulation in slices of rat cerebral cortex stimulated by either norepinephrine or phenylephrine. The failure of ECS to increase [3H]inositol 1-phosphate accumulation stimulated by phenylephrine, which is a partial agonist for this response, suggests that spare receptors do not account for the apparent absence of effect of ECS on alpha 1-adrenoceptor-mediated phosphoinositide hydrolysis.     

Age-Related Development of γ-Aminobutyric Acid (GABA)BReceptor Functions in Various Brain Regions of Spontaneously Hypertensive Rats

The age-related development of GABA_Breceptors and their coupling to adenylate cyclase were studied in the brains of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Compared with WKY rats, the specific [³H]GABA binding to GABA_Breceptors showed a significant decrease not only in the posterior hypothalamus, midbrain, hippocampus and striatum of eleven-week-old SHR, which maintain a hypertensive state, but also in the posterior hypothalamus of four-week-old normotensive SHR. Similarly, the GABA_Breceptor agonists (baclofen and DN-2327)-induced suppression of adenylate cyclase activity showed a decrease in the posterior hypothalamus of four-week-old SHR as well as in the posterior hypothalamus and striatum of eleven-week-old SHR. These results suggest that the functions of the GABA_Breceptor in the brain of SHR may be decreased independently from the occurrence of blood pressure elevation and that such changes may even be involved in the pathogenesis of SHR.     

自发性高血压大鼠中枢去甲肾上腺素与血管紧张...

The norepinephrine (NE) and angiotensin II (A II) contents in the brain regions of SHR and WKY (Wistar Kyoto) rats at different ages were determined by fluorospectrophotometry and radioimmunoassay. The systolic blood pressure (SBP) of the rats was measured indirectly with a tail cuff technique in conscious state. The results were as follows: There was no significant difference in the central A II and NE contents between SHR and WKY rats at 8-week age. Since 12th week age the SBP of SHR has increased gradually, up to 16th to 20th week and then maintained steady level. Whereas there was no significant change of SBP in WKY rats in the same span of age. In the early and late states of hypertension the A II contents in the medulla oblongata, pons, hypothalamus and nucleus caudatus of SHR were markedly higher than those of the age-matched WKY rats. But the change of NE content of SHR in the early stage showed a different picture as compared with that of WKY rats, i.e., NE decreased in medulla oblongata and anterior hypothalamus but increased in pons, posterior hypothalamus and nucleus caudatus. However, in the late stage there was no such significant difference between SHR and WKY rats. Consequently, it is suggested that the central A II and NE participated in the development of hypertension of SHR, and that the maintenance of hypertension is mainly dependent upon the increased A II content. Microinjection of captopril or 6-OHDA in the lateral cerebroventricle of SHR elicited a decrease of BP and reduction of both A II and NE contents in the medulla and hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Chronic Administration of Interferon α A/D on Serotonergic Receptors in Rat Brain

The effects of chronic administration of interferon (IFN; recombinant human IFN -A/D) on serotonergic binding sites in rat brain were investigated. IFN was injected daily for 2 weeks at a dose of 100000 I.U./kg, (i.p.) in male Wistar rats. IFN did not alter either [³H]ketanserin binding to 5-HT_2A receptors or [³H]paroxetine binding to 5-HT transporters. Scatchard analysis of [³H]8-hydroxy-dipropylaminotetraline (8-OH-DPAT) binding to 5-HT_1A receptors demonstrated the presence of high- and low-affinity binding sites in both treatment and control groups. IFN significantly increased both Kd and Bmax measures of [³H]8-OH-DPAT binding at low-affinity binding sites, but not at the high-affinity sites. These results suggest that IFN affects the low-affinity 5-HT_1A receptors sites and may be involved in the development of IFN-induced psychiatric disturbances.