Enhanced preganglionic sympathetic nerve responses in spontaneously hypertensive rats

Sympathetic nerve responses to posterior hypothalamic stimulation were recorded from the preceliac splanchnic nerve in spontaneously hypertensive rats (SHR) and normotensive, Wistar-Kyoto rats (WKY) following interruption of the baroreceptor reflex. Responses to identical stimulation were then recorded following ganglionic blockade with hexamethonium. The enhanced preganglionic sympathetic nerve responses measured in SHR indicate that the sympathetic hyperresponsiveness in this hypertensive strain occurs, at least in part, at a site within the central nervous system     

Maternal separation enhances neuronal activation and cardiovascular responses to acute stress in borderline hypertensive rats

There is much evidence suggesting early life events, such has handling or repeated separations from the nest, can have a long-term effect on the biological and behavioral development of rats. The current study examined the effect of repeated maternal separation (MS) on the behavioral, cardiovascular, and neurobiological responses to stress in subjects vulnerable to environmental stressors as adults. Borderline hypertensive rats (BHR), which are the first generation offspring of spontaneously hyperternsive and Wistar-Kyoto rats, were separated from the dams for 3h per day from postnatal day 1 through 14. Non-separated controls remained in the home cage. When allowed to explore the open field chamber for 60 min as adults, MS subjects had significantly greater locomotor activity compared to controls. All subjects were exposed to 30 min of restraint stress during which time mean arterial pressure (MAP) and heart rate (HR) were measured. Although both groups had comparable increases in MAP, MS animals displayed significantly higher HR throughout the stress period. Finally, MS subjects had significantly more stress-induced Fos positive cells, an estimate of neuronal activation, in the central nucleus of the amygdala (CeA), paraventricular nucleus of the hypothalamus (PVN), and the bed nucleus of the stria terminalis (BNST), each of which plays an important role in organizing the biobehavioral response to stress. These results suggest that maternal separation can further enhance stress reactivity in this model and may represent a useful approach for studying the relationship between early life events and future vulnerability to stressful situations.     

Balance among autonomic controls of heart rate in neonatal spontaneously hypertensive and borderline hypertensive rats

The ontogeny of functional sympathetic neural, adrenal medullary, and extra-adrenal components of adrenergic control of heart rate was compared in neonatal Spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and Borderline hypertensive (BHR) rats using combined sequential pharmacological blockade and surgical intervention. Baseline heart rate recorded from awake and unrestrained pups was lower in BHR than in WKY or SHR at 5 days of age. Tonic sympathetic neural control of heart rate was inferred from bradycardia after treatment with the adrenergic neuron-blocking agent, bretylium tosylate. Bradycardia after bretylium treatment was observed at 2, 5 and 8 days of age in all strains, suggesting tonic sympathetic neural control of heart rate during the first postnatal week. Parasympathetic control of heart rate was inferred from heart rate increase after treatment with the muscarinic receptor blocker, atropine methyl nitrate, in pups pretreated with bretylium. Tachycardia following atropine methyl nitrate was substantial in all 24-day-old pups. Control of heart rate by neurally mediated release of catecholamines from the adrenal medulla was inferred from bradycardia following administration of the ganglionic blocking agent, hexamethonium, to pups pretreated with bretylium and atropine methyl nitrate. Heart rate decreases after hexamethonium were found in 2-day-old WKY and BHR pups, and at 5 and 8 days in all strains. Adrenalectomy was performed in additional animals to confirm the adrenal catecholamine influence on heart rate. The influence of residual circulating catecholamines on neonatal heart rate was inferred from bradycardia following administration of the beta-adrenergic receptor blocking agent, atenolol, in pups pretreated with bretylium, methylatropine, and hexamethonium. Bradycardia was observed in pups of each strain and at all ages after atenolol treatment. Strain differences in autonomic controls of heart rate were most pronounced at 24 days of age. At 24 days of age both SHR and BHR pups showed increased adrenal catecholamine and parasympathetic influences on heart rate compared to WKY. Thus, prior to weaning, rats differing in their genetic predisposition to hypertension showed a unique pattern of autonomic control over heart rate which may be related to adult cardiovascular regulation.     

Role of prostaglandin,endothelin and sympathetic nervous system on the L-NAME-induced pressor responses in spontaneously hypertensive rats

We tested the hypothesis that in spontaneously hypertensive rat (SHR) NO produced centrally influences the resting arterial blood pressure by attenuating mechanisms involving prostaglandins, angiotensin II, endothelin and sympathetic nervous system. L-NAME (200 micro g/5 micro l), an inhibitor of NO synthase, administered intracerebroventricularly (i.c.v.) to awake and freely moving rats increased mean arterial blood pressure (MABP) in a biphasic pattern: an early transient increase within 1 min and a late prolonged response starting at 45 min and persisting for the duration of experiment (180 min). The two pressor responses involve different neurochemical mechanisms and, based on their latencies, they appear to reflect different anatomical sites of action of L-NAME. The late, but not the early pressor response, was prevented by pretreatment with chlorisondamine (2.5 mg/kg, i.v.), a ganglionic blocker, indicating its dependence on the sympathetic nervous system. Both pressor responses were abolished by i.c.v. pretreatment with indomethacin (200 micro g/5 micro l, i.c.v.), an inhibitor of cyclo-oxygenase, showing that they are mediated by prostaglandin(s). In contrast, losartan (25 micro g/5 micro l), an angiotensin II AT(1) receptor antagonist, had no effect. The initial pressor response was also attenuated by pretreatment with the endothelin ET(A)/ET(B) receptor antagonist, PD 145065 (48 micro g/2 micro l, i.c.v.). Intravenous pretreatment with another ET(A)/ET(B) receptor antagonist, L-754,142 (15 mg/kg as a bolus+15 mg/kg/h for 180 min), however, attenuated both responses to L-NAME. It is possible that L-754,142 crossed the blood-brain barrier and blocked, in addition, central ET(A)/ET(B) receptors. These studies show that NO synthesized in the brain attenuates pressor mechanisms involving prostaglandin, endothelin and sympathetic nervous system, but not angiotensin II, to modulate resting arterial blood pressure.     

Blood pressure and sympathetic activity in spontaneously hypertensive rats during food restriction

Summary Young (7 weeks) spontaneously hypertensive rats (SHR) were kept on food-restriction (33%) during 4 weeks with (0.3% saline as drinking water) or without sodium supplementation. Body weight and indirect systolic blood pressure (tail plethysmography) were followed each weak. During the last week of the intervention period 24 hour excretions of sodium, dopamine and nor-adrenaline were measured. Vascular pressor responses to noradrenaline were evaluated in pithed rats and the sympathetic nerve activity was assessed from the disappearance of endogenous noradrenline in the heart after synthesis inhibition. Despite a clear retardation of the growth rate in food-restricted rats the development of hypertension was not influenced. Food-restriction was associated with a moderate suppression of sympathetic activity. Furthermore, the vascular pressor responses to noradrenaline were decreased but this was reversed following sodium supplementation. It is concluded that despite evidence of sympathetic suppression weight reduction does not reduce the blood pressure in SHR once the blood pressure has started to rise.     

Norepinephrine content of discrete brain nuclei in acutely and chronically stressed borderline hypertensive rats

Forty-three male borderline hypertensive rats were subjected to either 3 days, or 4, 10, or 16 weeks of daily stress. An additional 43 animals served as unstressed, age-matched controls. At the end of study, animals were sacrificed, brains were removed, and cardiovascularly-important nuclei in the brainstem and hypothalamus were removed by micropunch. Assays revealed that norepinephrine (NE) levels were initially elevated in the brainstem in animals stressed for 3 days. As stress continued, NE levels were significantly lower in the brainstem, and eventually in the hypothalamus, of stressed animals. The relationship of these observations to environmentally-induced hypertension is discussed.     

Norepinephrine levels in discrete brain nuclei in borderline hypertensive rats exposed to compound stressors

The borderline hypertensive rat (BHR) appears to be an appropriate model for investigating the role of the environment in producing hypertension. Previous studies have demonstrated that the BHR shows chronic blood pressure elevations to both stress and high salt intake. Other studies suggest that interactions between the brain and kidney play an important role in initiating this hypertension. The central noradrenergic system has been implicated in these effects, especially in the hypothalamus. Because exercise has been found to attenuate stress-induced hypertension in the BHR, the current study sought to examine the impact of stressors paired with exercise (salt intake or stress) with those combining stress and high salt. Male BHR were exposed to either control, salt plus stress, salt plus exercise, or stress plus exercise conditions for either 2 or 6 months, beginning at 2 months of age. Following sacrifice, brain nuclei in the brain stem and hypothalamus were removed using the Palkovits micropunch technique. Punches were analyzed for NE content via liquid chromatography with electrochemical detection. Compared with the control condition, chronic salt plus stress led to reductions in NE content, especially in the hypothalamus. Compared with salt plus stress, the exercise conditions were associated with elevated NE levels, especially in the early phases of exposure to the treatment. The possible role of exercise training in preventing a central nervous system trigger from inducing hypertension in the BHR is discussed.     

Association between sympathetic nerve activity and cerebrovascular protection in young spontaneously hypertensive rats

The purpose of this study was to determine resting and maximal superior cervical sympathetic nerve activity in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) at five and ten weeks of age as hypertension was developing. Basal cervical sympathetic nerve activity (SNA) of five week SHR was 58 +/- 3 muv* which was significantly elevated over age-matched WKY (SNA = 30 +/- 4 muv, *p less than 0.001) and ten week SHR (SNA = 30 +/- 4 muv, *p less than 0.001) as well as ten week WKY (SNA = 24 +/- 4 muv, *p less than 0.001). Thus, during basal conditions five week SHR nerve traffic was approximately two times that found in age-matched WKY as well as in ten week SHR and WKY. The peak sympathetic nerve activity in response to rapid hemorrhage in five week SHR (215 +/- 16 muv*) was significantly elevated over the maximal response of WKY (140 +/- 23 muv) (*p less than 0.02). Ten week SHR also reached a maximal sympathetic nerve activity (187 +/- 28 muv*) that was significantly elevated over WKY (100 +/- 15 muv) (*p less than 0.02). Thus, both five and ten week SHR had a greater capacity for elevated nerve activity following rapid hemorrhage than age-matched WKY. The elevation in resting cervical sympathetic activity in five week SHR, and the elevated capacity for sympathetic neural response in both five as well as ten week SHR, are consistent with a central nervous system abnormality in SHR that could relate to the previously described protective influence of sympathetic nerves on SHR cerebral blood vessels as hypertension is developing.     

Differential alterations in sympathetic neurotransmission in mesenteric arteries and veins in DOCA-salt hypertensive rats

Sympathetic control of arteries and veins may be altered in hypertension. To test this hypothesis, constrictions of mesenteric arteries and veins caused by nerve stimulation and by norepinephrine (NE) and ATP were studied in vitro in tissues from deoxycorticosterone acetate (DOCA)-salt hypertensive and sham normotensive rats. In DOCA-salt arteries, the maximum neurogenic response was greater than that in sham arteries. The P2 receptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 10 microM), greatly reduced neurogenic responses in sham but not DOCA-salt arteries. The alpha1-adrenergic receptor antagonist, prazosin (0.1 microM), inhibited responses in DOCA-salt but not sham arteries. Concentration-response curves for norepinephrine and ATP were similar in sham and DOCA-salt arteries, indicating that reactivity to sympathetic vasoconstrictor transmitters was not changed in DOCA-salt arteries. Neurogenic constrictions in sham and DOCA-salt veins were similar in amplitude, and they were completely blocked by prazosin. However, concentration-response curves for norepinephrine in DOCA-salt veins were right-shifted compared to those in sham veins. Cocaine (10 microM) and corticosterone (10 microM) caused a leftward shift in norepinephrine concentration-response curves in DOCA-salt but not sham veins. Norepinephrine content was decreased in DOCA-salt arteries and veins, and there was an increased norepinephrine transporter (NET) level in DOCA-salt veins. These data indicate that, in DOCA-salt hypertension, there is an increased norepinephrine release from sympathetic nerves associated with mesenteric arteries and veins. In arteries, this results in an increase in the amplitude of neurogenic constrictions. In veins, increased norepinephrine release maintains neurogenic constrictions in the presence of increased NET levels.     

Baroreceptor reflex effect on sympathetic nerve activity in stroke-prone spontaneously hypertensive rats

To elucidate the relationship between responses in sympathetic outflow to incremental changes in blood pressure, we performed baroreflex activation experiments in conscious, stroke-prone, spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats. We gave incremental bolus injections of nitroprusside and methoxamine and measured mean blood pressure (MAP), heart rate, and splanchnic nerve activity (SpNA). Change in heart rate per change in blood pressure was greater in WKY rats than in SHRSP indicating the decrease in baroreceptor sensitivity displayed in the latter strain. In contrast, change in SpNA per change in blood pressure was greater in SHRSP than in WKY rats. These findings suggest that sympathetic outflow in SHRSP is more reactive to blood pressure changes than in WKY rats. The discordance in heart rate and SpNA changes supports the notion that central neural integration of autonomic function in SHRSP is impaired.     

Hypothalamic paraventricular nucleus inhibition decreases renal sympathetic nerve activity in hypertensive and normotensive rats

Activity of the hypothalamic paraventricular nucleus (PVN) is essential for the maintenance of vasomotor sympathetic nerve discharge (SND) and blood pressure even in the anesthetized rat. Inactivation of the paraventricular nucleus results in a large depressor and sympathoinhibitory response. The current study was designed to examine the regulation of renal sympathetic nerve activity by the paraventricular nucleus in both hypertensive and normotensive rats. Experiments were performed in anesthetized, artificially ventilated spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats. Renal sympathetic nerve activity, blood pressure and heart rate were recorded. Bilateral microinjections of the GABA(A) receptor agonist, muscimol (1 nmol in 100 nl), were made into the paraventricular nucleus. Decreases in blood pressure (SHR: from 111+/-3 to 54+/-4 mm Hg; WKY: 84+/-2 to 48+/-3 mm Hg), heart rate (SHR: 336+/-8 to 289+/-12 bpm; WKY 309+/-7 to 258+/-13 bpm) and renal sympathetic nerve activity (to 46+/-11% and 33+/-7% of control in the WKY and SHR, respectively) were observed. The renal nerve response to inactivation of the paraventricular nucleus was not different between the strains, indicating that modulation of renal sympathetic nerve activity by the paraventricular nucleus is similar in these rat strains. This is different from the previously reported effect of paraventricular nucleus inhibition on lumbar sympathetic nerve activity [Hypertension 39 (2002) 275]. Overall, we demonstrate that the paraventricular nucleus plays a critical role in the regulation of renal SND even under basal conditions in anesthetized animals.     

Electrophysiological effects of tachykinin agonists on sympathetic ganglia of spontaneously hypertensive rats

This study investigated the cellular basis for the enhanced ganglionic responsiveness to NK1 agonists in the spontaneously hypertensive rat (SHR) in comparison to their normotensive counterpart, the Wistar-Kyoto (WKY) rat. Rats for in vivo studies were anesthetized with pentobarbital and treated with chlorisondamine (10.5 micromol/kg). Extracellular recordings from the external carotid nerve showed a greater responsiveness of decentralized SHR superior cervical ganglia (SCG) to intravenous injection of SP (32 nmol/kg). Blood pressure and heart rate were increased in SHRs, whereas WKY rats responded with a decrease in blood pressure and only slight tachycardia. Membrane properties of SCG neurons, as shown by intracellular microelectrode recordings, were similar between strains. Picospritzer application of the NK1 agonist GR-73632 (100 microM, 1 s) evoked slow depolarization and increased neuron excitability. Spontaneous firing was evoked only in some neurons. Depolarization amplitudes were similar between strains; however, the NK1 agonist depolarized a greater number of neurons in hypertensive rats. In conclusion, SHRs are more responsive to ganglion stimulation by NK1 agonists due to a greater number of responsive cells within the SCG rather than an enhanced responsiveness of individual neurons.     

Dissociation of autonomic controls of heart rate in weaning-aged borderline hypertensive rats by perinatal NaCl

The ontogeny of functional sympathetic neural, adrenal medullary, and extra-adrenal components of adrenergic control of heart rate was investigated in borderline hypertensive rats exposed to either high or low sodium chloride (NaCl) from conception through weaning. Borderline hypertensive rats were produced by mating spontaneously hypertensive females with normotensive Wistar-Kyoto males. Females were maintained on diets containing either low (0.12% NaCl) or high (3% NaCl) dietary NaCl throughout pregnancy and lactation. At 28 days of age, baseline heart rates recorded from awake and unrestrained pups did not differ between low and high NaCl-exposed pups. Overall sympathetic tone, inferred from heart rate change after beta 1-adrenergic blockade with atenolol, did not differ between high and low NaCl-exposed pups. Early NaCl exposure did not alter the neural component of sympathetic control of heart rate as inferred from heart rate decrease after bretylium tosylate. Parasympathetic nervous system control, as reflected by tachycardic response to muscarinic receptor blockade with atropine methyl nitrate was also unchanged by early NaCl exposure. The adrenal catecholamine component of sympathetic control of heart rate was inferred from bradycardia following administration of the ganglion blocking agent, chlorisondamine, to pups pretreated with bretylium and atropine methyl nitrate. Pups exposed to low NaCl showed increased adrenal control of heart rate compared to high NaCl-exposed pups. The influence of residual catecholamines on heart rate was inferred from bradycardia following administration of the beta 1-adrenergic receptor blocking agent, atenolol, in pups pretreated with bretylium, atropine methyl nitrate, and chlorisondamine. Residual catecholamine influence was greater in rats exposed to high NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction of chronic non-inflammatory widespread pain increases cardiac sympathetic modulation in rats

Fibromyalgia (FM) is characterized by chronic non-inflammatory widespread pain (CWP) and changes in sympathetic function. In attempt to elucidate the pathophysiological mechanisms of FM we used a well-established CWP animal model. We aimed to evaluate changes in cardiac autonomic balance and baroreflex function in response to CWP induction in rats. CWP was induced by two injections of acidic saline (pH 4.0, n=8) five days apart into the left gastrocnemius muscle. Control animals were injected twice with normal saline (pH 7.2, n=6). One day after the second injection of acidic saline or normal saline, the animals had pulse interval (PI) and systolic arterial pressure (SAP) variability, and spontaneous baroreflex sensitivity (BRS) evaluated. After induction of CWP, there was an increase of power in the low frequency (LF) band of PI spectrum (12.75 ± 1.04 nu), a decrease in the high frequency (HF) band (87.25 ± 1.04 nu) and an increase of LF/HF ratio (0.16 ± 0.01), when compared to control animals (7.83 ± 1.13 nu LF; 92.16 ± 1.13 nu HF; 0.08 ± 0.01 LF/HF). In addition, there was an increase of power in the LF band of SAP spectrum (7.93 ± 1.39 mmHg(2)) when compared to control animals (2.97 ± 0.61 mmHg(2)). BRS was lower in acidic saline injected rats (0.59 ± 0.06 ms/mmHg) when compared to control animals (0.71 ± 0.03 ms/mmHg). Our results showed that induction of CWP in rats shifts cardiac sympathovagal balance towards sympathetic predominance and decreases BRS. These data corroborate findings in humans with FM.     

Analysis of cerebrovascular sympathetic nerve density in relation to stroke development in spontaneously hypertensive rats

Previous studies have shown that elevating the K+ levels from 0.75% to 2.11% in the diet of stroke-prone spontaneously hypertensive rats significantly retards the development of stroke and increases their lifespan. On the other hand, stroke-resistant spontaneously hypertensive rats fail to develop stroke even if they are fed the low-K+ version of this diet. Since sympathetic nerves surrounding the cerebral vasculature play an important role in protecting the brain from stroke during hypertension, I studied whether changes in sympathetic nerve density accounted for the differing incidences of stroke in stroke-prone spontaneously hypertensive rats fed high- and low-K+ diets and in stroke-resistant and stroke-prone spontaneously hypertensive rats fed a low-K+ diet. At 14 weeks of age, all 11 stroke-prone rats fed the low-K+ diet had evidence of cerebral hemorrhage while such lesions were virtually absent in the 11 littermates fed the high-K+ diet and totally absent in the eight stroke-resistant rats fed the low-K+ diet. Stroke-prone (regardless of diet) but not stroke-resistant rats exhibited greater sympathetic nerve densities in the left hemisphere than in the right. When stroke-prone rats were compared, in some areas of the cerebrovasculature, rats fed the high-K+ diet had greater mean sympathetic nerve densities than those fed the low-K+ diet. On the other hand, stroke-resistant and stroke-prone rats fed the low-K+ diet exhibited comparable sympathetic nerve densities in most cerebral arteries studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reactive oxygen species in paraventricular nucleus modulates cardiac sympathetic afferent reflex in rats

Our previous studies showed that angiotensin II (Ang II) in the paraventricular nucleus (PVN) potentiated the cardiac sympathetic afferent reflex (CSAR) in rats. This study investigated whether the reactive oxygen species (ROS) in the PVN modulated the CSAR and contributed to the effect of Ang II on the CSAR in rats. Under alpha-chloralose and urethane anesthesia, renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate were recorded in sinoaortic-denervated and cervical-vagotomized rats. The CSAR was evaluated by the RSNA response to epicardial application of bradykinin (0.04 and 0.4 mug). Compared with microinjection of saline into the PVN, superoxide anion scavenger, either tempol (20 nmol) or tiron (10 nmol), significantly decreased the CSAR (P < 0.05). Conversely, superoxide dismutase (SOD) inhibitor diethyldithio-carbamic acid (DETC, 10 nmol) potentiated the CSAR (P < 0.05). Microinjection of Ang II (0.3 nmol) into the PVN resulted in an enhanced CSAR (P < 0.05). The effect of Ang II on the CSAR was completely inhibited by pretreatment with either tempol or tiron (P < 0.05) but was not affected by DETC. On the other hand, either tempol or tiron decreased the RSNA (P < 0.05), but DETC increased the RSNA (P < 0.05). Ang II increased the RSNA (P < 0.05) and MAP (P < 0.05). The effect of Ang II on the RSNA and MAP was abolished by pretreatment with either tempol or tiron but was not affected by DETC. These results indicated that the ROS in the PVN modulated the CSAR and contributed to the effect of Ang II in the PVN on the CSAR.     

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.     

Structural and neurochemical features of postganglionic sympathetic neurons in the superior mesenteric ganglion of spontaneously hypertensive rats

Postganglionic sympathetic neurons, which are exquisitely sensitive to small changes in levels of target-derived nerve growth factor (NGF), express two transmembrane receptors: 1) the trkA receptor mediates neuron survival and neurite outgrowth; and 2) the p75 neurotrophin receptor (p75NTR) enhances neuronal responsiveness of trkA to NGF. Elevating levels of NGF induces several morphological and neurochemical alterations in sympathetic neurons, including axonal sprouting, increased levels of p75NTR mRNA relative to trkA mRNA, and increased accumulations of NGF in hypertrophied somata. Spontaneously hypertensive rats (SHR) display both elevated NGF levels and increased sympathetic axonal innervation of the mesenteric vasculature. In this investigation we assessed whether sympathetic neurons innervating the mesenteric vasculature of SHR display other features indicative of increased levels of target-derived NGF. In 5-week-old SHR, levels of both p75NTR and trkA mRNA in mesenteric sympathetic neurons were significantly elevated compared to levels in age-matched control rats. By 15 and 30 weeks of age, levels of p75NTR mRNA expression in mesenteric sympathetic neurons were similar between SHR and control rats. Accumulations of NGF were depleted in the sympathetic somata of 15- and 30-week-old SHR compared to age-matched control rats. Moreover, sympathetic neurons in SHR were not hypertrophied, as the sizes of somata were comparable between SHR and control rats. Our data illustrate that despite having augmented levels of NGF in the mesenteric vasculature, SHR do not display many of the morphological and neurochemical features that are associated with an enhanced responsiveness by sympathetic neurons to elevated levels of target-derived NGF.     

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.