Similar poststimulatory pressor responses with different mechanisms in response to excitation of the locus coeruleus before and after acute adrenalectomy

Electrical stimulation of the locus coeruleus in anesthetized rats evoked a biphasic pressor response consisting of an initial sharp rise in blood pressure at the onset of stimulation, followed by a second elevation after cessation of the stimulus. This response, which was accompanied by an increase in plasma noradrenaline and adrenaline levels, was stable and could be easily reproduced over time. Sympathectomy by administration of guanethidine selectively abolished the primary pressor response. beta-Adrenergic blockade by intravenous administration of sotalol enhanced the secondary pressor response without affecting the primary component. Adrenal demedullation performed 24-48 h before the experiments selectively prevented the secondary pressor component. In contrast, acute adrenalectomy carried out during the experiment to impair the adrenomedullary secretions eliminated the secondary pressor response to stimulation of the locus coeruleus only in sympathectomized or in sotalol-treated rats but not in intact rats in which the response persisted. The latter, however, could be abolished by the administration of either guanethidine or sotalol, and it disappeared following repeated stimulation of the locus coeruleus. The study demonstrates that similar poststimulatory pressor responses with different underlying mechanisms can be elicited on excitation of the locus coeruleus before and after acute adrenalectomy in the rat. The results also suggest that intraneuronal adrenaline may be involved in the response evoked in acutely adrenalectomized animals.     

Peripheral and central mechanisms of the pressor response elicited by stimulation of the locus coeruleus in the rat

Electrical stimulation of the pontine nucleus locus coeruleus (LC) caused an increase of the arterial blood pressure in anesthetized rats, and elevated plasma noradrenaline (NA) and adrenaline (A) levels. The stimulation-induced pressor response was characteristically biphasic and consisted of a sharp rise in arterial pressure at the onset of the stimulation, followed by a second elevation at the end of the stimulus. Bilateral adrenalectomy or adrenal demedullation completely blocked the secondary phase of the pressor response elicited by stimulation, but did not affect the primary phase. The latter was specifically eliminated by the destruction of the peripheral sympathetic vasomotor axons with intravenous 6-hydroxydopamine (6-OHDA). The active sites eliciting the secondary adrenomedullary pressor component appeared to be restricted to the nucleus LC, whereas the primary sympathetic vasomotor response could be elicited from sites in and around the nucleus. After brain transection at the midbrain level, stimulation of LC failed to evoke the adrenomedullary pressor response, while the sympathetic vasomotor component was not affected. Similarly, destruction of brain NA neurons by intraventricular administration of 6-OHDA did not change the sympathetic vasomotor response, but virtually abolished the adrenal response. The results demonstrate that the pressor response to stimulation of LC in the rat is due to both increased sympathetic vasomotor activity and CA released from the adrenal medulla. The study also provides evidence suggesting that the noradrenergic LC cell group play an important role in the activation of the adrenal medulla, but is not essential for the activation of the sympathetic vasoconstrictor fiber system.     

Adrenomedullary secretory response to midbrain stimulation in rat: effects of depletion of brain catecholamines or serotonin

Electrical stimulation of the periaqueductal gray substance (PAG) of the rostral midbrain of the rat produced biphasic or monophasic pressor responses depending on the duration of the stimulus train. Marked increases in plasma noradrenaline (NA) and adrenaline (A) levels accompanied the pressor responses, indicating the participation of the adrenal medulla. Depletion of central catecholamines (CA) by intraventricular administration of 6-hydroxydopamine (6-OHDA) did not affect the primary vasomotor component but markedly depleted adrenal CA levels and attenuated the adrenomedullary component of the response to brain stimulation. The intraperitoneal administration of p-chlorophenylalanine (pCPA) not only depleted brain serotonin (5-HT) levels but also reduced brain CA levels significantly. The adrenaline (A) levels were reduced in the adrenal glands of these rats and the adrenal secretory response to brain stimulation was attenuated. In contrast, the selective destruction of central 5-HT neurons by intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) in rats pretreated with desmethylimipramine (DMI) did not influence either the pressor nor the plasma CA responses to brain stimulation. Furthermore, the adrenal glands of these rats were normal. The results suggest that: (i) the central catecholaminergic neurons play an important role in the regulation of the adrenal glands but are not essential for the activation of the sympathetic vasoconstrictor fiber system: (ii) the pressor and plasma CA responses to PAG stimulation are not dependent on the central serotonergic system.     

Reflex pressure response to the electric stimulation of different parts of the rat stomach

The role of the autonomic nervous system in the pressor response to the electrical stimulation of different gastric zones has been studied in rats. The stimulus was applied before and after the following interventions: bilateral vagotomy, ganglionic blockade, alpha-adrenergic receptor blockade and beta-adrenergic receptor blockade. After the ganglionic blockade no pressor responses to the electrical stimulus were observed. After the alpha-adrenergic blockade a lower pressor response was observed. A hypertensive response can be induced by mechanical, chemical or electrical stimulation of gastric receptors. It is concluded that the pressor reflex following the application of an electrical stimulus on different zones of the digestive tract is mediated by the sympathetic nervous system and that the efferent pathways are mainly alpha-adrenergic ones.     

Stimulation of NTS A1 adenosine receptors evokes counteracting effects on hindlimb vasculature

Our previous studies concluded that stimulation of the nucleus of the solitary tract (NTS) A2a receptors evokes preferential hindlimb vasodilation mainly via inducing increases in preganglionic sympathetic nerve activity (pre-ASNA) directed to the adrenal medulla. This increase in pre-ASNA causes the release of epinephrine and subsequent activation of beta-adrenergic receptors that are preferentially located in the skeletal muscle vasculature. Selective activation of NTS A1 adenosine receptors evokes variable, mostly pressor effects and increases pre-ASNA, as well as lumbar sympathetic activity, which is directed to the hindlimb. These counteracting factors may have opposite effects on the hindlimb vasculature resulting in mixed vascular responses. Therefore, in chloralose-urethane-anesthetized rats, we evaluated the contribution of vasodilator versus vasoconstrictor effects of stimulation of NTS A1 receptors on the hindlimb vasculature. We compared the changes in iliac vascular conductance evoked by microinejctions into the NTS of the selective A1 receptor agonist N6-cyclopentyladenosine (330 pmol in 50 nl volume) in intact animals with the responses evoked after beta-adrenergic blockade, bilateral adrenalectomy, bilateral lumbar sympathectomy, and combined adrenalectomy + lumbar sympathectomy. In intact animals, stimulation of NTS A1 receptors evoked variable effects: increases and decreases in mean arterial pressure and iliac conductance with prevailing pressor and vasoconstrictor effects. Peripheral beta-adrenergic receptor blockade and bilateral adrenalectomy eliminated the depressor component of the responses, markedly potentiated iliac vasoconstriction, and tended to increase the pressor responses. Lumbar sympathectomy tended to decrease the pressor and vasoconstrictor responses. After bilateral adrenalectomy plus lumbar sympathectomy, a marked vasoconstriction in iliac vascular bed still persisted, suggesting that the vasoconstrictor component of the response to stimulation of NTS A1 receptors is mediated mostly via circulating factors (e.g., vasopressin, angiotensin II, or circulating catecholamines released from other sympathetic terminals). These data strongly suggest that stimulation of NTS A1 receptors exerts counteracting effects on the iliac vascular bed: activation of the adrenal medulla and beta-adrenergic vasodilation versus vasoconstriction mediated by neural and humoral factors.     

Exercise pressor reflex in decerebrate and anesthetized rats

I investigated whether muscular contraction evokes cardiorespiratory increases (exercise pressor reflex) in alpha-chloralose- and chloral hydrate-anesthetized and precollicular, midcollicular, and postcollicular decerebrated rats. Mean arterial pressure (MAP), heart rate (HR), and minute ventilation (Ve) were recorded before and during 1-min sciatic nerve stimulation, which induced static contraction of the triceps surae muscles, and during 1-min stretch of the calcaneal tendon, which selectively stimulated mechanosensitive receptors in the muscles. Anesthetized rats showed various patterns of MAP response to both stimuli, i.e., biphasic, depressor, pressor, and no response. Sciatic nerve stimulation to muscle in precollicular decerebrated rats always evoked spontaneous running, so the exercise pressor reflex was not determined from these preparations. None of the postcollicular decerebrated rats showed a MAP response or spontaneous running. Midcollicular decerebrated rats consistently showed biphasic blood pressure response to both stimulations. The increases in MAP, HR, and Ve were related to the tension developed. The static contractions in midcollicular decerebrated rats (381 +/- 65 g developed tension) significantly increased MAP, HR, and Ve from 103 +/- 12 to 119 +/- 24 mmHg, from 386 +/- 30 to 406 +/- 83 beats/min, and from 122 +/- 7 to 133 +/- 25 ml/min, respectively. After paralysis, sciatic nerve stimulation had no effect on MAP, HR, or Ve. These results indicate that the midcollicular decerebrated rat can be a model for the study of the exercise pressor reflex.     

Neuropeptide Y and control of vascular resistance in skeletal muscle

The effect of neuropeptide Y (NPY) on the increase in skeletal muscle vascular resistance caused by exogenous noradrenaline and by sympathetic stimulation was examined in gracilis muscles of anaesthetised dogs. NPY potentiated the increases in resistance caused by both of these to similar degrees. Although NPY itself often caused an elevation in the basal resistance, correlation coefficients for the percentage increase in basal resistance due to NPY and the percentage increase in the evoked sympathetic and noradrenergic responses in the presence of NPY indicated that it was the NPY itself (rather than the increase in basal resistance per se) which was responsible for the potentiation. The potentiation was apparently biphasic, with an initial peak in response during the first 20 min following administration of NPY followed by a secondary peak between 30 and 60 min. Radioimmunoassay for plasma levels of NPY indicated that the secondary increase of vascular resistance was not associated with a secondary peak in the plasma level of NPY.     

Neuropeptide Y co-exists and co-operates with noradrenaline in perivascular nerve fibers

Neuropeptide Y (NPY)-immunoreactive nerve fibers were numerous around arteries and few around veins. NPY probably co-exists with noradrenaline in such fibers since chemical or surgical sympathectomy eliminated both NPY and noradrenaline from perivascular nerve fibers and since double staining demonstrated dopamine-beta-hydroxylase, the enzyme that catalyzes the conversion of dopamine to noradrenaline, and NPY in the same perivascular nerve fibers. Studies on isolated blood vessels indicated that NPY is not a particularly potent contractile agent in vitro. NPY greatly enhanced the adrenergically mediate contractile response to electrical stimulation and to application of adrenaline, noradrenaline or histamine, as studied in the isolated rabbit gastro-epiploic and femoral arteries. The potentiating effect of NPY on the response to electrical stimulation is probably not presynaptic since NPY affected neither the spontaneous nor the electrically evoked release of [3H]noradrenaline from perivascular sympathetic nerve fibers.     

Sympathetic regulation of adrenal medullary function during aging

Our recent studies on changes in sympathoadrenal medullary function with age in anesthetized Wistar rats were reviewed. Although secretion rates of adrenaline and noradrenaline from the adrenal gland under resting conditions varied among animals, they gradually increased after 300 days and reached a level 2-4 times higher at 800-900 days compared with that of 100 days. Spontaneous activity of a single sympathetic nerve fiber under resting conditions also increased during aging in a manner similar to the catecholamine secretion rates. Reflex responses of mass activity of adrenal sympathetic nerve fibers to stimulation of baroreceptor and cutaneous mechanoreceptors were compared in young adult (4 months old) and aged (26 months old) Wistar rats under strictly controlled conditions for anesthesia, respiration and body temperature. Under these conditions the reflex depression in response to baroreceptor stimulation and cutaneous brushing as well as reflex excitation in response to cutaneous pinching were quite well maintained in the aged rats.     

Neuropeptide tyrosine (NPY)-induced potentiation of the pressor activity of catecholamines in conscious rats

IV bolus administration of 2.5-50 micrograms NPY (0.6-12.5 nmol) to conscious rats produced a dose- and time-dependent increase in systolic and diastolic blood pressure. Following priming with 2.5 micrograms NPY, or larger doses, the subsequent administrations of noradrenaline produced pressor responses that were potentiated both in magnitude and duration. The NPY-induced potentiation of the pressor response to noradrenaline was dose-dependent and extended to the pressor action of adrenaline and angiotensin II but not to the hypotensions produced by bradykinin or isoproterenol. The potentiation was not related to the fact that multiple doses of catecholamines were repeated. Reserpine did not substantially modify the NPY-induced potentiation of the pressor activity of the catecholamines. Chemical sympathectomy following 6-hydroxydopamine caused a marked supersensitivity to the catecholamines and NPY but obliterated the NPY-induced potentiation of the pressor effect of adrenaline. Nifedipine reduced the pressor action of the catecholamines and NPY but did not attenuate the NPY-induced potentiation of the pressor action of catecholamines. It is concluded that the acute pressor effect of NPY and of the potentiation of the catecholamine pressor effects involve different mechanisms.     

Chlordiazepoxide inhibition of reflex vagal bradycardia in the cat

The effect of chlordiazepoxide (CDZ) on phenylephrine-induced reflex vagal bradycardia was studied in cats anesthetized with chloralose. The sympathetic component of the reflex was eliminated by either pretreating the animals with propranolol (1 mg/kg, i.v.) or sectioning the spinal cord. In animals pretreated with propranolol, CDZ (3, 10 and 20 mg/kg, i.v.) produced a dose-related inhibition of phenylephrine-induced bradycardia. These doses of CDZ had no significant effect on phenylephrine-induced pressor responses. Similar results were obtained with CDZ in animals with spinal cords transected. Chlordiazepoxide did not prevent bradycardia evoked by electrical stimulation of the peripheral cut-end of the right vagus nerve. These results indicate that CDZ can inhibit reflex vagal bradycardia and that the inhibition involves a central action of the drug.     

ANG II in the paraventricular nucleus potentiates the cardiac sympathetic afferent reflex in rats with heart failure.

Chronic heart failure (CHF) is characterized by sympathoexcitation, and the cardiac sympathetic afferent reflex (CSAR) is a sympathoexcitatory reflex. Our previous studies have shown that the CSAR was enhanced in CHF. In addition, central angiotensin II (ANG II) is an important modulator of this reflex. This study was performed to determine whether the CSAR evoked by stimulation of cardiac sympathetic afferent nerves (CSAN) in rats with coronary ligation-induced CHF is enhanced by ANG II in the paraventricular nucleus (PVN). Under alpha-chloralose and urethane anesthesia, renal sympathetic nerve activity (RSNA) was recorded. The RSNA responses to electrical stimulation (5, 10, 20, and 30 Hz) of the CSAN were evaluated. Bilateral microinjection of the AT1-receptor antagonist losartan (50 nmol) into the PVN had no significant effects in the sham group, but it abolished the enhanced RSNA response to stimulation in the CHF group. Unilateral microinjection of three doses of ANG II (0.03, 0.3, and 3 nmol) into the PVN resulted in dose-related increases in the RSNA responses to stimulation. Although ANG II also potentiated the RSNA response to electrical stimulation in sham rats, the RSNA responses to stimulation after ANG II into the PVN in rats with CHF were much greater than in sham rats. The effects of ANG II were prevented by pretreatment with losartan into the PVN in CHF rats. These results suggest that the central gain of the CSAR is enhanced in rats with coronary ligation-induced CHF and that ANG II in the PVN augments the CSAR evoked by CSAN, which is mediated by the central angiotensin AT1 receptors in rats with CHF.     

Muscle pressor reflex: potential role of vanilloid type 1 receptor and acid-sensing ion channel.

Reflex cardiovascular responses to muscle contraction are mediated by mechanical and metabolic stimulation of thin muscle afferent fibers. Metabolic stimulants and receptors involved in responses are uncertain. Capsaicin depolarizes thin sensory afferent nerves that have vanilloid type 1 receptors (VR1). Among potential endogenous ligands of thin fibers, H+ has been suggested as a metabolite mediating the reflex muscle response as well as a potential stimulant of VR1. It has also been suggested that acid-sensing ion channels (ASIC) mediate H+, evoking afferent nerve excitation. We have examined the roles of VR1 and ASIC in mediating cardiovascular reflex responses to acid stimulation of muscle afferents in a rat model. In anesthetized rats, injections of capsaicin into the arterial blood supply of triceps surae muscles evoked a biphasic response (n = 6). An initial fall in mean arterial pressure (from baseline of 95.8 +/- 9.5 to 70.4 +/- 4.5 mmHg, P < 0.05 vs. baseline) was followed by an increase (to 131.6 +/- 11.3 mmHg, P < 0.05 vs. baseline). Anandamide (an endogenous substance that activates VR1) induced the same change in blood pressure as did capsaicin. The pressor (but not depressor) component of the response was blocked by capsazepine (a VR1 antagonist) and section of afferent nerves. In decerebrate rats (n = 8), H+ evoked a pressor response that was not blocked by capsazepine but was attenuated by amiloride (an ASIC blocker). In rats (n = 12) pretreated with resiniferatoxin to destroy muscle afferents containing VR1, capsaicin and H+ responses were blunted. We conclude that H+ stimulates ASIC, evoking the reflex response, and that ASIC are likely to be frequently found on afferents containing VR1. The data also suggest that VR1 and ASIC may play a role in processing of muscle afferent signals, evoking the muscle pressor reflex.     

Acid-sensing ion and epithelial sodium channels do not contribute to the mechanoreceptor component of the exercise pressor reflex

Amiloride, injected into the popliteal artery, has been reported to attenuate the reflex pressor response to static contraction of the triceps surae muscles. Both mechanical and metabolic stimuli arising in contracting skeletal muscle are believed to evoke this effect, which has been named the exercise pressor reflex. Amiloride blocks both acid-sensing ion channels, as well as epithelial sodium channels. Nevertheless, amiloride is thought to block the metabolic stimulus to the reflex, because this agent has been shown to attenuate the reflex pressor response to injection of lactic acid into the arterial supply of skeletal muscle. The possibility exists, however, that amiloride may also block mechanical stimuli evoking the exercise pressor reflex. The mechanical component of the reflex can be assessed by measuring renal sympathetic nerve activity during the first 2-5 s of contraction. During this period of time, the sudden tension developed by contraction onset briskly discharges mechanoreceptors, whereas it has little effect on the discharge of metaboreceptors. We, therefore, examined the effect of amiloride (0.5 microg/kg) injected into the popliteal artery on the renal sympathetic and pressor responses to static contraction of the triceps surae muscles in decerebrated cats. We found that amiloride significantly attenuated the pressor and renal sympathetic responses to contraction; for the latter variable, the attenuation started 10 s after the onset of contraction. Our findings lead us to conclude that acid-sensing ion channels and epithelial sodium channels play little, if any, role in evoking the mechanical component of the exercise pressor reflex.     

Multireceptor activation of the pulmonary chemoreflex

Schertel et al. (J. Appl. Physiol. 61: 1237-1240, 1984) reported that pulmonary C fibers initiate the prompt apnea followed by rapid shallow breathing evoked by pulmonary arterial injections of capsaicin. However, doubt has remained as to whether these changes in breathing pattern are induced exclusively by direct stimulation of pulmonary C fibers or whether secondary stimulation of slowly adapting pulmonary stretch receptors by capsaicin-induced reflex bronchoconstriction also contributes to the response. To determine the contribution of this secondary mechanism to changes in breathing pattern, we evoked the pulmonary chemoreflex in spontaneously breathing dogs before and after blockade of muscarinic receptors with atropine. Right atrial injections of capsaicin before the administration of atropine induced a classical pulmonary chemoreflex, i.e., apnea, hypotension, and bradycardia followed by rapid shallow breathing and bronchoconstriction. After atropine, all components of the pulmonary chemoreflex induced by right atrial injections of capsaicin remained intact except bronchoconstriction. However, the absolute magnitude of the change in each component of the reflex except apnea was significantly attenuated. We conclude that the classic pulmonary chemoreflex is a complex phenomenon initiated primarily by stimulation of pulmonary C fibers but significantly influenced by secondary stimulation of slowly adapting pulmonary stretch receptors.     

室旁核在剌激猫肾神经传入纤维引起的血压效应中的应用

The purpose of this study is to investigate the role of paraventricular nucleus of the hypothalamus (PVN) and alpha 1 adrenergic receptor of PVN in the pressor responses to stimulation of renal afferent nerve in alpha 1-chloralose-anesthetized cats with carotid sinoaortic denervation and vagotomy. The pressor response to stimulation of renal afferent nerve consisted of a primary and a second components. The primary component response was completely blocked while the second component was not blocked by autonomic blocking agents (hexomethonium and atropine). Bilateral lesions of PVN greatly attenuated the pressor response before and after autonomic blockade. Intracerebroventricular and PVN injection alpha 1, adrenergic antagonist (prazosin) significantly decreased in the pressor response to stimulation of renal afferent nerve. These results indicate that paraventricular nucleus of the hypothalamus and alpha 1 adrenergic receptors in central nervous system, especially in PVN, play an important role in the pressor responses to stimulation of renal afferent nerve.     

Centrally acting leptin induces a resuscitating effect in haemorrhagic shock in rats

Centrally acting leptin induces the activation of the sympathetic nervous system with a pressor effect in normotensive rats. The purpose of the study was to examine central leptin-evoked action in critical haemorrhagic hypotension. In anaesthetized male Wistar rats subjected for irreversible haemorrhagic shock with mean arterial pressure (MAP) 20-25 mmHg haemodynamic parameters and plasma concentrations of adrenaline and noradrenaline were measured. Leptin given intracerebroventricularly (20 μg) evoked long-lasting rises in MAP and heart rate (HR), with a subsequent increase in renal, mesenteric and hindquarters blood flows and a 100% survival at 2 h. MAP and peripheral blood flow changes were inhibited by a pre-treatment with α(1)- and α(2)-adrenoceptor antagonists prazosin (0.5 mg/kg) and yohimbine (1 mg/kg), while β-adrenoceptor antagonist propranolol (1 mg/kg) blocked leptin-induced HR changes, without influence on MAP, peripheral blood flows and survival. Twenty min after leptin treatment, there were higher plasma concentrations of noradrenaline, but not adrenaline, in comparison with the saline-treated control group. In conclusion, centrally acting leptin induces a long-lasting pressor effect with an improvement in the survival rate in haemorrhage-shocked rats. The effect may be associated with the activation of the sympathetic nervous system.     

Blockade of purinergic 2 receptors attenuates the mechanoreceptor component of the exercise pressor reflex

The finding that pyridoxalphosphate-6-azophenyl-2,4-disulfonic acid (PPADS), a P2 antagonist, attenuated the pressor response to calcaneal tendon stretch, a purely mechanical stimulus, raises the possibility that P2 receptors sensitize mechanoreceptors to static contraction of the triceps surae muscles. The mechanical component of the exercise pressor reflex, which is evoked by static contraction, can be assessed by measuring renal sympathetic nerve activity during the first 2-5 s of this maneuver. During this period of time, group III mechanoreceptors often discharge explosively in response to the sudden tension developed at the onset of contraction. In decerebrated cats, we, therefore, examined the effect of PPADS (10 mg/kg) injected into the popliteal artery on the renal sympathetic and pressor responses to contraction and stretch. We found that PPADS significantly attenuated the renal sympathetic response to contraction, with the effect starting 2 s after its onset and continuing throughout its 60-s period. PPADS also significantly attenuated the renal sympathetic nerve response to stretch, but did so after a latency of 10 s. Our findings lead us to conclude that P2 receptors sensitize group III muscle afferents to contraction. The difference in the onset latency between the PPADS-induced attenuation of the renal sympathetic response to contraction and the renal sympathetic response to stretch is probably due to the sensitivities of different populations of group III afferents to ATP released during contraction and stretch.     

Chemical sympathectomy with 6-hydroxydopamine potentiates intracerebroventricularly applied bombesin-induced increase in plasma adrenaline

Intracerebroventricular administration of bombesin induced a marked increase in plasma level of adrenaline and a slight increase in that of noradrenaline in rats anesthetized with urethane. The bombesin-induced increase in adrenaline was potentiated by chemical sympathectomy with 6-hydroxydopamine (6-OHDA). On the other hand, adrenalectomy did not affect plasma level of noradrenaline in the bombesin-treated animals. In the splanchnicotomized rats, direct stimulation of the adrenal glands by intravenously administered nicotine increased plasma level of both adrenaline and noradrenaline. These increases were, however, not potentiated by chemical sympathectomy with 6-OHDA. Pretreatment with capsaicin, a potent toxin selective to sensory neurons, potentiated the bombesin-induced increase in plasma level of adrenaline. In these capsaicin pretreated rats, chemical sympathectomy did not potentiate the bombesin-induced increase in plasma level of adrenaline to any great extent. These results suggest that chemical sympathectomy with 6-OHDA potentiated the bombesin-induced increase in plasma adrenaline probably due to a disinhibitory activation of the splanchnic nerve by as yet unidentified but capsaicin sensitive neuron mechanisms.     

Neuromedin U causes biphasic cardiovascular effects and impairs baroreflex function in rostral ventrolateral medulla of spontaneously hypertensive rat

Neuromedin U (NMU) causes biphasic cardiovascular and sympathetic responses and attenuates adaptive reflexes in the rostral ventrolateral medulla (RVLM) and spinal cord in normotensive animal. However, the role of NMU in the pathogenesis of hypertension is unknown. The effect of NMU on baseline cardiorespiratory variables in the RVLM and spinal cord were investigated in urethane-anaesthetized, vagotomized and artificially ventilated male spontaneously hypertensive rats (SHR) and Wistar–Kyoto rats (WKY). Experiments were also conducted to determine the effects of NMU on somatosympathetic and baroreceptor reflexes in the RVLM of SHR and WKY. NMU injected into the RVLM and spinal cord elicited biphasic response, a brief pressor and sympathoexcitatory response followed by a prolonged depressor and sympathoinhibitory response in both hypertensive and normotensive rat models. The pressor, sympathoexcitatory and sympathoinhibitory responses evoked by NMU were exaggerated in SHR. Phrenic nerve amplitude was also increased following intrathecal or microinjection of NMU into the RVLM of both strains. NMU injection into the RVLM attenuated the somatosympathetic reflex in both SHR and WKY. Baroreflex sensitivity was impaired in SHR at baseline and further impaired following NMU injection into the RVLM. NMU did not affect baroreflex activity in WKY. The present study provides functional evidence that NMU can have an important effect on the cardiovascular and reflex responses that are integrated in the RVLM and spinal cord. A role for NMU in the development and maintenance of essential hypertension remains to be determined.