Acute and chronic restraint stress: effects on [I]-galanin binding in normotensive and hypertensive rat brain

The neuropeptide galanin (GAL) has been implicated in the neural response to a number of stressors including restraint; however, the effect of restraint stress on GAL receptor density in the central nervous system (CNS) has not been investigated. Normotensive (Wistar-Kyoto; WKY) and hypertensive (spontaneously hypertensive; SHR) rats were subjected to a daily 60-min restraint stress paradigm for 0 (control), 1, 3, 5 or 10 consecutive days, and the density of [¹²⁵I]-GAL binding sites following exposure to restraint was compared between strains using quantitative autoradiography. Significant differences in basal (no stress) levels of GAL receptor density between WKY and SHR were detected in regions such as the central nucleus of the amygdala (Ce) and ventromedial hypothalamus (VMH) (P<0.05). In WKY, restraint stress (1 day) induced significant decreases in GAL receptor density in forebrain regions such as the Ce (−41%) and medial nucleus of the amygdala (−41%) (P<0.05). Chronic restraint (10 days) did not induce significant decreases in these nuclei in WKY, indicating that forebrain neurons containing GAL receptors in WKY possessed a functional ability to adapt to repeated restraint. In addition, restraint stress induced significant decreases in GAL receptor density in SHR in regions such as the lateral parabrachial nucleus (−43%; 5 days of restraint) and hypoglossal nucleus (−18% for entire restraint period) (P<0.05). In conclusion, restraint stress resulted in region- and strain-specific alterations in GAL receptor density, some of which may contribute to the altered stress response previously observed in hypertensive rats. The results clearly support the hypothesis that neuropeptides such as GAL are an integral component of the neural response to psychological stress, although the functional significance of the changes in GAL receptor density described in this study awaits elucidation.     

Measurement of immunoreactive angiotensin II levels in microdissected brain nuclei from developing spontaneously hypertensive and Wistar Kyoto rats

Levels of immunoreactive angiotensin II (ANG II) were measured in specific microdissected nuclei from the brains of newborn (NB; less than 1 week of age), 4-, 8-, and 12-week-old spontaneously hypertensive rats (SHR) and their age-matched normotensive controls, Wistar Kyoto (WKY) rats, using a sensitive radioimmunoassay. The structures investigated included the paraventricular nucleus of the hypothalamus (PVH), the nucleus of the solitary tract (NTS), the dorsal motor nucleus of the vagus (DMN of X), the locus coeruleus (LC), and the A1 region of the medulla. A section of cerebellar cortex was used as a control. Although ANG II was detected in each of the nuclei examined, there were no differences in the ANG II contents of any of these structures between young (NB and 4 week old) SH and WKY rats. However, by 8 weeks of age, the SHR had significantly higher ANG II levels in the PVH, NTS, and DMN of X than its normotensive control, and at 12 weeks of age, significantly higher ANG II levels were observed in the PVH, NTS, DMN of X, and LC of the SHR compared to those in the WKY. During the developmental period under investigation, both strains revealed increases in the ANG II content of all nuclei except for the LC, where the ANG II levels decreased with age. No detectable ANG II was found in the cerebellar cortex of either strain at any age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decreases in the expression of CGRP and galanin mRNA in central and peripheral neurons related to the control of blood pressure following experimental hypertension in rats

Calcitonin gene-related peptide (alpha CGRP) and galanin (GAL) are peptides known to participate in central mechanisms of blood pressure control. Nonetheless, variations in the synthesis of the peptides in response to a hypertensive challenge are not well described, specially using a model, which allows acute and chronic analyses. In this study, we have employed in situ hybridization to analyse changes in mRNA expression of alpha CGRP and GAL in the nucleus tractus solitarii (NTS), hypothalamic paraventricular nucleus (PVN) as well as petrosal and nodose ganglia after aortic coarctation-induced hypertension in rats. Acute (2h) and chronic (3 and 7 days) analyses were performed in order to evaluate the involvement of both peptides in different periods of hypertension. The analysis of relative mRNA levels showed significant differences between sham-operated and aortic coarcted hypertensive rats. alpha CGRP mRNA expression was decreased 2h (40%) and 3 days (42%) in nodose and petrosal ganglia, respectively, after coarctation. No changes in CGRP mRNA signal were seen in the NTS and PVN in the analysed periods. GAL mRNA expression was decreased in the NTS (19%) and PVN (55%), 3 and 7 days, respectively, after coarctation-induced hypertension. No changes in GAL mRNA expression were observed in petrosal and nodose ganglia following aortic coarctation. Data suggest that alpha CGRP and GAL may participate in the mechanisms involved in the establishment/maintenance of hypertension induced by aortic coarctation. Acute changes might be involved with the adaptation to the hypertensive state, while changes at the chronic phase might be related to counteraction of hypertension.     

Participation of endogenous galanin in the suppression of baroreceptor reflex response by locus coeruleus in the rat

We evaluated the potential participation of endogenous brain galanin (GAL) in the suppression of baroreceptor reflex (BRR) response by locus coeruleus (LC), using adult male Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p., with 15 mg/kg/h i.v. infusion supplements). Our physiologic and pharmacologic results demonstrated that bilateral microinjection of GAL antiserum (1:20, 20 n1) into the nucleus tractus solitarii (NTS), the terminal site for baroreceptor afferent fibers, significantly attenuated the suppressive effect of LC on the BRR response. Pretreatment with the same amount of normal rabbit serum (1:20) or heat-inactivated GAL antiserum (1:20), on the other hand, was ineffective. Microinjection of GAL (100 pmol) into the bilateral NTS also appreciably depressed the BRR response. Histochemically, retrogradely labeled neurons were distributed in the LC following microinjection of fast blue into the NTS. Immunofluorescent staining further revealed that some of these fast blue labeled LC neurons also showed positive immunoreactivity to GAL. These results suggest that a direct galaninergic projection to the NTS may participate in the suppression of BRR response by the LC.     

Ultrastructural studies on catecholaminergic terminals and GABAergic neurons in nucleus tractus solitarius of the rat medulla oblongata

Synaptogenesis of catecholamine (CA) boutons in the nucleus tractus solitarius (NTS) was compared between spontaneously hypertensive (SHR) rats and Wistar-Kyoto (WKY) rats at different ages. On the average, there were about 32 CA varicosities per 2200 μm² area of the NTS in both SHR and WKY rats as revealed by glyoxylic acid fluorescence microscopic (FM) morphometric study. The FM analysis indicated that there were no significant changes in the CA varicosity density between SHR and WKY rats.The CA boutons were labeled with 5-hydroxydopamine and appeared to contain small granular vesicles at the electron microscopic (EM) level. A total of 1402 CA boutons were studied in a 540, 000 μm² area of the NTS. The number of CA boutons involved in synaptic contacts vs the number of total CA boutons was used to obtain synaptic frequency which was taken as an index for synaptogenesis. A reduction of approximately 18% and 14% of synaptogenesis of CA boutons was observed in the NTS of SHR rats at 4 weeks (prehypertensive stage) and 12 weeks (early hypertensive stage) of age respectively, as compared to age-matched WKY rats. No significant difference of synaptogenesis of CA neurons was found between SHR and WKY rats at 16 weeks of age, a stage in which hypertension is well established and maintained in SHR rats. These results suggest that CA neurons with fewer synaptic contacts in the NTS may play a more important role in the initiation than in the maintenance of hypertension in the SHR rats.In addition to CA terminals, there were numerous GABAergic cell bodies in the NTS which were identified by immunocytochemistry using antibodies to the GABA synthesizing enzyme,l-glutamate decar☐ylase (GAD). GABAergic dendrites with GAD-positive reaction were often seen to receive several GAD-negative synapses at EM random profiles. In the text, a viewpoint is thus discussed that emphasizes that a synaptic abnormality of CA terminals with fewer synaptic contacts affecting GABAergic neurons may participate in the pathogenesis of hypertension. However, it remains to be determined as to whether or not there is a direct contact between CA boutons and GABAergic dendrites.     

Increased anti-apoptotic conditions in the nucleus tractus solitarii of spontaneously hypertensive rat

Since the nucleus tractus solitarii (NTS) is a pivotal region for regulating the set-point of arterial pressure, we propose here its role in the development of neurogenic hypertension. Given the findings of recent studies suggesting that the NTS of spontaneously hypertensive rats (SHR) exhibits a specific inflammatory state characterized by leukocyte accumulation within the NTS microvasculature, we hypothesized that gene expression levels of apoptotic factors are altered in the NTS of SHR compared to normotensive Wistar-Kyoto rats (WKY). To test this hypothesis, we used RT(2) Profiler PCR arrays targeting apoptosis-related factors. We found that gene expression of the death receptor Fas (tumor necrosis factor receptor superfamily, member 6) and the cysteine-aspartic acid protease caspase 12 were down-regulated in the NTS of both adult hypertensive and young pre-hypertensive SHR compared to age-matched WKY. On the other hand, an anti-apoptotic factor, neuronal apoptosis inhibitory protein, was highly increased in the NTS of SHR. These results suggest that the NTS of SHR exhibits an anti-apoptotic condition. Furthermore, this profile appears not to be secondary to hypertension. Whether this differential gene expression in the NTS contributes to the hypertensive state of the SHR via alteration of neuronal circuitry regulating cardiovascular autonomic activity awaits elucidation.     

Paramedian reticular nucleus--sympathetic inhibition in spontaneously hypertensive rats

The cardiovascular reactivity of various areas in the medulla related to sympathetic or parasympathetic activation, or to sympathetic inhibition, was compared in spontaneously hypertensive rats (SHR) and in normotensive rats Wistar-Kyoto (WKY) or Sprague-Dawley (SD). In SHR, which has an elevated resting systemic arterial blood pressure (SAP), the sympathetic pressor responses elicited from electrical stimulation of the dorsomedial medulla (DMM), parvocellular lateral nucleus (PVC) or ventrolateral medulla (VLM) were more profound than those in WKY and SD. The depressor and bradycardia responses elicited from electrical stimulation of the paramedian reticular nucleus (PRN) (which exerts both sympathetic and parasympathetic inhibitions) or from the area of the solitary nucleus/dorsomotor nucleus of vagus (NTS/DMV) (where stimulation leads to both parasympathetic activation and sympathetic inhibition) were also more intensive in SHR than in WKY and SD. The elicited pressor and depressor responses, however, were not significantly different between WKY and SD. Our results are consistent with previous findings (15) that in SHR an increased sympathetic activity of the pressor areas of medulla contributes to the pathogenesis of hypertension. Sympathetic inhibition (PRN and NTS/DMV areas) and parasympathetic activation (NTS/DMV area) from these areas, however, may not be critically involved.     

Enhanced serotonin-mediated responses in the nucleus tractus solitarius of spontaneously hypertensive rats

Previous studies have demonstrated that injection of serotonin into the nucleus tractus solitarius (NTS) elicits hypotension and bradycardia in rats. The present study sought to further characterize this response and to examine the role of serotonergic mechanisms in the NTS in cardiovascular regulation in spontaneously hypertensive (SHR) rats. Injections of picomole amounts of serotonin into the NTS of chloralose-anesthetized normotensive Sprague-Dawley (S-D) or Wistar-Kyoto (WKY) rats produced hypotension and bradycardia that were eliminated by prior injection into the NTS of the selective 5HT(2) antagonist sarpogrelate. Bilateral injection of sarpogrelate did not alter blood pressure or reflex changes in heart rate in response to phenylephrine-induced increases in blood pressure or nitroprusside-induced decreases in blood pressure. In SHR rats, the depressor response produced by injection of serotonin into the NTS was markedly larger than in WKY rats, and was larger than depressor responses previously reported for other excitatory substances injected into the NTS. In SHR rats bilateral injection of sarpogrelate produced an increase in blood pressure, although it did not alter baroreceptor-evoked changes in heart rate. These results provide further support for the hypothesis that stimulation of 5HT(2) receptors in the NTS contributes to cardiovascular regulation independent of the baroreceptor reflex. Furthermore, this serotonergic system is altered in SHR rats, apparently acting tonically to reduce blood pressure.     

Enhanced angiotensin-mediated responses in the nucleus tractus solitarii of spontaneously hypertensive rats

Studies using an AT(1) receptor antagonist, losartan, demonstrated that depressor and bradycardic responses to angiotensin II (Ang II) injection into the nucleus tractus solitarii (NTS) are mediated via those receptors. We further characterized Ang II-evoked cardiovascular responses in this nucleus in spontaneously hypertensive rats (SHR) using a new, selective AT(1) receptor antagonist, valsartan. In alpha-chloralose-anesthetized Sprague-Dawley (S-D) rats, Wistar-Kyoto (WKY) rats, and SHR, unilateral injection of Ang II into the NTS decreased arterial pressure (AP) and heart rate (HR). This response was eliminated by preinjection of valsartan. Depressor responses were much greater in SHR than in WKY rats. In normotensive rats, bilateral valsartan injection did not alter baseline AP or HR, or baroreceptor reflex index (BRI) calculated as the maximal change in HR (bpm) divided by phenylephrine- or nitroprusside-induced maximal change in mean AP (mmHg). In SHR, this treatment did not alter baseline HR and BRI, but significantly increased AP. Preinjection of valsartan did not alter injected glutamate effects in any strain. Thus, stimulation of AT(1) receptors within the NTS contributes to cardiovascular regulation independently of the baroreceptor reflex and the glutamatergic system. This angiotensinergic system in SHR acts tonically to reduce AP.     

Increased GABA<Subscript>B</Subscript> Receptor Subtype Expression in the Nucleus of the Solitary Tract of the Spontaneously Hypertensive Rat

Expression of GABA(B) receptor messenger RNA (mRNA) in the central nervous system was compared between the spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rat. Polymerase chain reaction (PCR) revealed all the isoforms except B1e in cortex, hypothalamus, and medulla oblongata. In the nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM), the B1a-c and 1 g isoforms were present as well as B2. Real-time PCR detected significantly higher levels of B1a (p < 0.01) and B2 (p < 0.05) mRNA in the NTS of SHR compared to WKY. A significant increase in B1a expression (p < 0.05) was detected in VLM. Immunolabeling suggested presynaptic and postsynaptic expression of B1a, B1b, and B2 subtypes throughout the NTS, with significant differences in distribution patterns and labeling between subtypes and between SHR and WKY. These findings suggest that GABA(B) receptors expressed by neurones in NTS may be involved in cardiovascular regulation and that changes in GABA(B) mRNA expression levels may contribute to the hypertensive state in SHR.     

Functional subdivisions of the nucleus tractus solitarii of the rat as determined by circulatory and respiratory responses to electrical stimulation of the nucleus

We have recently identified two functional subdivisions of the nucleus tractus solitarii (NTS) in the cat: the pressor and apneustic (inspiratory) response zone, and the depressor and apneic (hypopneic) response zone. The presence of such functional subdivisions in the NTS of the rat was explored. The circulatory and respiratory responses to electrical stimulation of a small part of the NTS were surveyed in all regions of the NTS in rats anesthetized with urethane (500 mg/kg, i.p.). A set of depressor, bradycardiac and apneic responses was elicited in the dorsomedial portions, whereas a pressor response with or without an apneic (hypopneic) response was elicited in the ventral and lateral portions. The presence of a difference in the functional subdivisions between spontaneously hypertensive rats (SHR) and normotensive rats (WKY) was also explored. The SHR group showed significantly larger pressor responses than the WKY group (P less than 0.001), despite its higher basal level of arterial blood pressure, but significantly fewer bradycardiac responses (P less than 0.001). This suggests the SHR group is more sensitive in terms of sympathetic vasomotor activity but less sensitive in parasympathetic cardioinhibitory activity. There was no significant difference in the distribution of the pressor and depressor response zones between the two strains.     

α2-Adrenergic receptor distribution and density within the nucleus tractus solitarii of normotensive and hypertensive rats during development

The nucleus tractus solitarii (NTS), located in the brainstem, is one of the main nuclei responsible for integrating different signals in order to originate a specific and orchestrated autonomic response. Antihypertensive drugs are well known to stimulate alpha(2)-adrenoceptor (alpha(2R)) in brainstem cardiovascular regions to induce reduction in blood pressure. Because alpha(2R) impairment is present in several models of hypertension, the aim of the present study was to investigate the distribution and density of alpha(2R) binding within the NTS of Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats during development (1,15,30 and 90 day-old) by an in vitro autoradiographical study. The NTS shows heterogeneous distribution of alpha(2R) in dorsomedial/dorsolateral, subpostremal and medial/intermediate subnuclei. Alpha(2R) increased from rostral to caudal dorsomedial/dorsolateral subnuclei in 30 and 90 day-old SHR but not in WKY. Alpha(2R) decreased from rostral to caudal subpostremal subnucleus in 15, 30 and 90 day-old SHR but not in WKY. Medial/intermediate subnuclei did not show any changes in alpha(2R) according to NTS levels. Furthermore, alpha(2R) are decreased in SHR as compared with WKY in all NTS subnuclei and in different ages. Surprisingly, alpha(2R) impairment was also found in pre-hypertensive stages, specifically in subpostremal subnucleus of 15 day-old rats. Finally, alpha(2R) decrease from 1 to 90 day-old rats in all subnuclei analyzed. This decrease is different between strains in rostral dorsomedial/dorsolateral and caudal subpostremal subnuclei within the NTS. In summary, our results highlight the importance of alpha(2R) distribution within the NTS regarding the neural control of blood pressure and the development of hypertension.     

Acute and chronic restraint stress: effects on [125I]-galanin binding in normotensive and hypertensive rat brain

The neuropeptide galanin (GAL) has been implicated in the neural response to a number of stressors including restraint; however, the effect of restraint stress on GAL receptor density in the central nervous system (CNS) has not been investigated. Normotensive (Wistar-Kyoto; WKY) and hypertensive (spontaneously hypertensive; SHR) rats were subjected to a daily 60-min restraint stress paradigm for 0 (control), 1, 3, 5 or 10 consecutive days, and the density of [125I]-GAL binding sites following exposure to restraint was compared between strains using quantitative autoradiography. Significant differences in basal (no stress) levels of GAL receptor density between WKY and SHR were detected in regions such as the central nucleus of the amygdala (Ce) and ventromedial hypothalamus (VMH) (P<0.05). In WKY, restraint stress (1 day) induced significant decreases in GAL receptor density in forebrain regions such as the Ce (-41%) and medial nucleus of the amygdala (-41%) (P<0.05). Chronic restraint (10 days) did not induce significant decreases in these nuclei in WKY, indicating that forebrain neurons containing GAL receptors in WKY possessed a functional ability to adapt to repeated restraint. In addition, restraint stress induced significant decreases in GAL receptor density in SHR in regions such as the lateral parabrachial nucleus (-43%; 5 days of restraint) and hypoglossal nucleus ( approximately -18% for entire restraint period) (P<0.05). In conclusion, restraint stress resulted in region- and strain-specific alterations in GAL receptor density, some of which may contribute to the altered stress response previously observed in hypertensive rats. The results clearly support the hypothesis that neuropeptides such as GAL are an integral component of the neural response to psychological stress, although the functional significance of the changes in GAL receptor density described in this study awaits elucidation.     

Gene expression profiles of major cytokines in the nucleus tractus solitarii of the spontaneously hypertensive rat

Since the nucleus of the solitary tract (NTS) is a pivotal region for regulating the set-point of arterial pressure, we proposed a role for it in the development of neurogenic hypertension. Recent studies have suggested that pro-inflammatory molecules are highly expressed in the NTS of an animal model of human essential hypertension--the spontaneously hypertensive rat (SHR), compared to normotensive Wistar-Kyoto rat (WKY). Based on this evidence, we hypothesized that inflammatory mediators such as cytokines are up-regulated in the hypertensive NTS. In the present study, we have assessed the level of gene expression of some cytokines in the NTS of SHR compared to WKY. In addition, for further confirmation of abnormal inflammatory condition within the NTS of SHR, we identified gene expression levels of an inflammatory marker, glycoprotein-39 (gp39) precursor, which is homologous to chitinase 3-like protein 1, human cartilage-gp39 or YKL40. The NTS was micro-dissected from 15-week-old male SHR and WKY rats. Total RNA was extracted and quantitative RT-PCR was performed. Gene expression of gp39 precursor and monocyte chemoattractant protein-1 were higher in the NTS of SHR while inter-leukin-6 was lower in the NTS of SHR compared to the WKY. In contrast, there were no significant differences in the expression of other cytokines including: inter-leukin-1 beta, tumor necrosis factor-alpha and transforming growth factor beta 1. These data together with our previous published finding of an over expression of junctional adhesion molecule-1 suggest that the NTS of the SHR exhibits a specific inflammatory state.     

Specific inflammatory condition in nucleus tractus solitarii of the SHR: novel insight for neurogenic hypertension?

Human essential hypertension is a complex polygenic trait with underlying genetic components that remain unknown. Since the brainstem structure--the nucleus of the solitary tract (NTS)--is a pivotal region for regulating the set-point of arterial pressure, we proposed a role for it in the development of primary hypertension. Using microarray and real-time RT-PCR, we have recently identified that some pro-inflammatory molecules, such as junctional adhesion molecule-1 (JAM-1; a leukocyte/platelet adhesion molecule), were over expressed in endothelial cells in the NTS of an animal model of human essential hypertension--the spontaneously hypertensive rat (SHR) compared to normotensive Wistar Kyoto rats (WKY). Adenoviral mediated over expression of JAM-1 in NTS of WKY rats produced both hypertension and localized leukocyte adherence to the microvasculature. With a known effect of leukocyte adhesion causing cytokine release, we predicted differences in the level of gene expression of cytokines in the NTS of SHR relative to WKY. Gene expression of monocyte chemoattractant protein-1 (MCP-1) was higher in the NTS of SHR while inter-leukin-6 (IL-6) was lower in the NTS of SHR compared to the WKY. Because both inflammatory molecules are known to affect neural functions, our data suggest that the microvasculature of NTS of the SHR exhibits a specific inflammatory state. We propose a new hypothesis that as a consequence of enhanced expression of leukocyte adhesion molecules within the microvasculature of NTS there is a specific inflammatory response that leads to cardiovascular autonomic dysfunction contributing to neurogenic hypertension.     

Localization of AT(2) receptors in the nucleus of the solitary tract of spontaneously hypertensive and Wistar Kyoto rats using [125I] CGP42112: upregulation of a non-angiotensin II binding site following unilateral nodose ganglionectomy

We have examined the binding distribution of a selective AT(2) receptor ligand [125I] CGP42112 in the brain of adult Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). AT(2) receptor localization was also examined in the rat brainstem following unilateral nodose ganglionectomy. Specific [125I] CGP42112 binding was observed in discrete brain regions from both rat strains, including the nucleus of the solitary tract (NTS), and did not differ between WKY and SHR. [125I] CGP42112 binding in the NTS revealed an AT(2) receptor component that was displaceable by PD 123319 and Ang II (50-58%), as well as a non-angiotensin II receptor component (42-49%). Following unilateral nodose ganglionectomy, [125I] CGP42112 binding density on the denervated side of the NTS was increased approximately two-fold in both WKY and SHR. This increased [125I] CGP42112 binding density in the ipsilateral NTS was comprised of a greater non-angiotensin II component than that observed in the sham groups, since only approximately 30% was displaced by PD123319 and angiotensin II. Furthermore, [125I] CGP42112 also revealed high binding density on the denervated side in the dorsal motor nucleus and the nucleus ambiguus in both WKY and SHR. AT(2) receptor immunoreactivity was also visualised in the NTS of sham operated rats, but was not observed in the dorsal motor nucleus or the nucleus ambiguus, nor was it up-regulated following nodose ganglionectomy. These results demonstrate, for the first time, an AT(2) receptor binding site in the NTS, as well as a non-angiotensin II [125I] CGP42112 binding site. These studies also demonstrate that nodose ganglionectomy represents a useful model in which to study a non-angiotensin II [125I] CGP42112 binding site that is up-regulated following degeneration of afferent vagal nerves.     

Yohimbine-induced alterations of monoamine metabolism in the spontaneously hypertensive rat. I. The peripheral nervous system

The effects of alpha 2 adrenoreceptor blockade with YOH on blood pressure, plasma catecholamines and norepinephrine (NE) stores in kidney, adrenal and spleen of spontaneously hypertensive rats of the Okamoto strain (SHR) and Wistar-Kyoto (WKY) control animals were examined. YOH administration resulted in a significant (p less than 0.001) reduction in arterial pressure in both SHR and WKY. Plasma NE and EPI were significantly (p less than 0.05) elevated by YOH treatment in both SHR and WKY, but SHR exhibited a significantly (p less than 0.05) greater percent increase in plasma NE than WKY. YOH produced significant decreases in splenic NE content in both SHR and WKY but reduced renal NE content in the SHR only. SHR had significantly higher basal renal NE and DA content and fewer NE uptake (3H-desmethylimipramine binding) sites (p less than 0.05) than WKY. Treatment of SHR or WKY with either the alpha 2-adrenergic antagonist, idazoxan, or the alpha 1-antagonist, prazosin, failed to significantly alter renal NE levels from those found after saline injection. The enhanced YOH-induced renal NE depletion in SHR suggests an alteration in the presynaptic control of NE release in the genetically hypertensive rat, however, the effects of YOH in the SHR may be mediated by mechanisms unrelated to alpha 2-adrenergic receptors.