Effect of dermorphin and morphine on the sympathetic and cardiovascular system of the pithed rat

Dermorphin is a recently discovered opioid peptide which is unique in having a D-amino acid in its sequence. Dermorphin binding sites have been shown in central and peripheral organs and central administered dermorphin produces profound autonomic responses. The purpose of this study was to examine the effect of intravenous dermorphin on heart rate and blood pressure of the pithed rat in basal condition and in response to controlled sympathetic stimulation. Also, since dermorphin is a selective mu-receptor agonist, its effects were compared to morphine, an opiate selective for mu receptors. Dermorphin (0.0001-10 mumol/kg, i.v) or morphine (1-10 mg/kg) had no effect on basal heart rate or blood pressure and failed to modify sympatho-adreno-medullary evoked pressor and tachycardic responses. Furthermore, dermorphin or morphine did not affect the increase in plasma norepinephrine and epinephrine in response to spinal cord stimulation. It is concluded that the dermorphin and morphine have no direct peripheral effects on heart rate or blood vessel tone nor do these mu-receptor agonists have any effect on norepinephrine and epinephrine release from the sympathetic nerves and the adrenal medulla in the rat.     

Decreases in blood pressure in response to L-Glutamate microinjections into the A5 catecholamine cell group

Electrical stimulation of the A5 region in the rat has been shown to elicit a rise in blood pressure with no change in heart rate²⁵. However, electrical stimulation excites axons of passage as well as cell bodies. To activate A5 cells more selective, we have stimulated them with monosodium-l-glutamate.Thel-glutamate was pressure injected from one barrel of a double-barrelled pipette. The other barrel, filled with Agar/KCl, was used for electrical stimulation. In midbrain-hemisected rats, electrical stimulation of the A5 region elicited a pressor response with no change in heart rate, as before. However, 30 nl microinjections ofl-glutamate led to a dose-related decrease in blood pressure and heart rate. The threshold for the depressor response was about 10 mMl-glutamate, and a maximal depressor response of 30 mm Hg was elicited at about 500 mM.To determine if either the pressor or depressor response involved catecholamines, these experiments were repeated in midbrain-hemisected animals whose central noradrenergic and dopaminergic axon terminals were destroyed with intraventricular 6-hydroxydopamine. While the pressor response to electrical stimulation was still present in these animals, the bradycardic and depressor responses tol-glutamate injection were abolished.Finally, the bradycardic and depressor responses were markedly reduced in animals that had been sympathectomized with guanethidine.These results suggest that activation of A5 cells leads to a decrease in blood pressure and heart rate brought about mainly through the sympathetic nervous system.     

Acute administration of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a selective 5-HT-receptor agonist,causes a biphasic blood pressure response and a bradycardia in the normotensive Sprague-Dawley rat and in the spontaneously hypertensive rat

Summary 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) is a new serotonin (5-HT) receptor agonist that binds selectively to the 5-HT_1A binding site. In the present paper we investigated the cardiovascular effects of 8-OH-DPAT in the normotensive Sprague-Dawley rat and in the spontaneously hypertensive rat. The acute i.v. administration of 8-OH-DPAT (5–150g/kg) was in both rat strains associated with a biphasic blood pressure response and a bradycardia. The initial pressor response was due to a direct vascular effect of 8-OH-DPAT involving activation of-adrenoceptors since it was present in pithed rats and in reserpine pretreated rats and since it was attenuated by prazosin. The longer lasting hypotension was not due to a direct vascular relaxation or a presynaptic inhibition of transmitter release since the hypotension was not evident in pithed rats and since 8-OHDPAT did not influence the pressor responses to electrical stimulation in pithed rats. Rather, the combination of hypotension and bradycardia would suggest a central site of action although the intracerebroventricular (lat. ventricles) route of administration was not more efficient (to induce hypotension) than i.v. administration. At least the bradycardia was mediated by changes in vagal as well as sympathetic discharge since it was prevented by pretreatment with atropine and propranolol in combination but not by pretreatment with either agent alone. The cardiovascular effects of 8-OH-DPAT were not prevented by pretreatment with methergoline, methiothepin, pirenperone or cianserine or by 5-HT depletion by means of p-chlorophenylalanine, which suggests that the putative 5-HT receptor that is responsible for the hypotension and bradycardia to 8-OH-DPAT is not of a presynaptic type and does not have the pharmacological characteristics of a general 5-HT₁ receptor.     

Chronic 5-HT2 receptor blockade with ritanserin does not reduce blood pressure in the spontaneously hypertensive rat

Summary Chronic oral treatment (8 weeks) with the selective 5-hydroxytryptamine₂ (5-HT₂)-receptor blocking agent, ritanserin, did not reduce blood pressure in the spontaneously hypertensive rat (SHR) during basal conditions or during stress (jet air). In pithed rats the pressor responses to 5-HT but not to phenylephrine or sympathetic stimulation of the sympathetic outflow were completely antagonized. These observations indirectly suggests that the 5-HT₂-receptor blocking properties of the antihypertensive agent ketanserin cannot alone account for the antihypertensive effects in SHR that are observed during chronic treatment with this agent.     

The involvement of the anterior cingulate cortex in blood pressure control

The visceromotor nature of the rat anterior cingulate cortex was investigated by electrically stimulating this area in both anesthetized and awake animals. Initial studies demonstrated that electrical stimulation of any division of the anterior cingulate cortex elicits a significant fall in blood pressure in the sodium pentobarbital-anesthetized rat. Depressor responses were greatest (up to 50% decreases) following stimulation of the ventral third of the anterior cingulate cortex. Heart rate was not altered by cingulate cortex stimulation. In the awake animal, stimulation of previously identified depressor sites in the rostral third of the pregenual cingulate cortex elicited pressor responses. In contrast, stimulation of the caudal third of this cortex elicited depressor responses, and stimulation of the middle third elicited biphasic (pressor followed by depressor) responses. These results indicate that the anterior cingulate cortex is a visceromotor region which may provide a cortical output for the regulation of blood pressure responses associated with learning and or stress.     

Autonomic nerve and cardiovascular responses to changing blood oxygen and carbon dioxide levels in the rat

Contribution of autonomic nervous system activity to the heart rate and blood pressure responses during chemoreceptor excitations by systemic hypoxia and hypercapnia and to hyperoxia and hypocapnia was analyzed in the urethane-anesthetized, artificially ventilated rats. Systemic hypoxia induced a co-activation of two antagonistic nerves: an increase in cardiac sympathetic and in cardiac vagal efferent nerve discharges. Increased heart rate was due to predominance of the cardiac sympathetic over the cardiac vagal activation. In spite of a marked reflex increase in the renal and cardiac sympathetic nerve activities, the local vasodilator effect of hypoxia prevented consistent changes in arterial blood pressure. Bilateral section of the carotid sinus nerves (CSN) mostly abolished autonomic nerve responses and produced a profound decreases in the blood pressure during hypoxia. Hyperoxia elicited a pressor response due to peripheral vasoconstriction with no significant change in the autonomic nerve activities except for a decrease in the cardiac sympathetic nerve discharges. Hypercapnia significantly increased blood pressure and renal nerve sympathetic activity. In contrast to hypoxia, hypercapnia excited cardiac sympathetic and inhibited cardiac vagal activity. This reciprocal effect did not elicit neurogenic cardioacceleration, because it was masked by the local inhibitory action of CO2 on the heart rate. The increase in sympathetic activities and in blood pressure during hypercapnia persisted after bilateral CSN section indicating that the responses were mediated by central rather than by peripheral chemoreceptors. Hypocapnia produced a significant increase in cardiac vagal discharges yet a cardioacceleratory response occurred due to the local effect upon heart rate. The present results indicate that in the rat, autonomic nervous responses differ depending on the type, i.e. hypoxic or hypercapnic, chemoreceptor stimuli. Reflex heart rate and blood pressure responses do not follow the autonomic nerve activities exactly. Circulatory responses are greatly modified by local peripheral effects of hypoxic, hyperoxic, hypocapnic or CO2 stimuli on the cardiovascular system. Species differences characterizing the autonomic nerve responsiveness to chemical stimuli in the rat are described.     

Pressor effects of electrical stimulation of medial prefrontal cortex in unanesthetized rats

The medial prefrontal cortex (MPFC) is involved in central nervous system (CNS)-mediated cardiovascular modulation. We compared the cardiovascular effects of electrical stimulation (EE) of the MPFC in unanesthetized rats to those observed after stimulation of the same area in urethane-anesthetized rats. Electrical stimulation (35, 106, 177, 247, 318, and 389 microA rms/10 sec, 60-Hz sine wave) of the MPFC of urethane-anesthetized rats caused depressor responses of stimulus-related intensity. The cardiovascular response to electrical stimulation of the MPFC in unanesthetized rats was characterized by stimulus-related pressor responses. No significant heart rate changes were observed during the EE period in any case. The pressor response to electrical stimulation (106 microA rms/10 sec, 60-Hz sine wave) of the MPFC was not affected by intravenous pretreatment with the vasopressin antagonist dTyr(CH(2))(5)(Me)AVP (50 microg/kg, intravenously), by hypophysectomy, or by intravenous pretreatment with the angiotensin II antagonist losartan (1 mg/kg, intravenously). The pressor response was blocked by intravenous pretreatment with the ganglionic blocker mecamylamine (2 mg/kg, intravenously) but was not affected by adrenal demedullation, thus suggesting involvement of the neural component of the sympathetic nervous system without a major involvement of its hormonal component. Our results confirmed the occurrence of depressor responses after electrical stimulation of the MPFC in urethane-anesthetized rats and evidenced that only pressor responses are observed after its stimulation in unanesthetized rats. The fact that the pressor response to the stimulation of the MPFC was blocked by a ganglioplegic suggests that the MPFC has functional excitatory actions over the sympathetic nervous system.     

Cardiovascular responses to glutamate microinjection in the dorsomedial periaqueductal gray of unanesthetized rats

The periaqueductal gray area (PAG) is a mesencephalic area involved in cardiovascular modulation. Glutamate (L‐Glu) is an abundant excitatory amino acid in the central nervous system (CNS) and is present in the rat PAG. Moreover, data in the literature indicate its involvement in central blood pressure control. Here we report on the cardiovascular effects caused by microinjection of L‐Glu into the dorsomedial PAG (dmPAG) of rats and the glutamatergic receptors as well as the peripheral mechanism involved in their mediation. The microinjection of L‐Glu into the dmPAG of unanesthetized rats evoked dose‐related pressor and bradycardiac responses. The cardiovascular response was significantly reduced by pretreatment of the dmPAG with a glutamatergic M‐methyl‐D‐aspartate (NMDA) receptor antagonist (LY235959) and was not affected by pretreatment with a non‐NMDA receptor antagonist (NBQX), suggesting a mediation of that response by the activation of NMDA receptors. Furthermore, the pressor response was blocked by pretreatment with the ganglion blocker pentolinium (5 mg/kg, intravenously), suggesting an involvement of the sympathetic nervous system in this response. Our results indicate that the microinjection of L‐Glu into the dmPAG causes sympathetic‐mediated pressor responses in unanesthetized rats, which are mediated by glutamatergic NMDA receptors in the dmPAG. © 2012 Wiley Periodicals, Inc.     

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.     

Role of neuropeptide Y (NPY) in cardiovascular responses to stress

Neuropeptide Y (NPY), a putative sympathetic neurotransmitter and neuromodulator, is released during sympathetic nerve stimulation and causes vasoconstriction and cardiodepression. Whether the release of NPY contributes to stress-induced cardiovascular responses was assessed by studying i/ plasma levels of circulating NPY-immunoreactivity (NPY-ir) during various stress paradigms and ii/ mechanisms of action of NPY in the cardiovascular system of the rat. Plasma NPY-ir was increased by all stress situations, such as transfer to a new environment (by 52%), exposure to cold water (4⁰C) (by 117%) and hemorrhage (4 ml/300 g body weight) (by 231%). The cold water, stressinduced, maximal increase in circulating plasma NPY-ir was delayed in relation to the peak pressor response by 10–20 min. Administration of NPY caused dose-dependent pressor responses that were greater in pithed rats - which have all centrally mediated circulatory reflexes removed - than in conscious rats. Infusion of a low pressor (8.5 ± 1.5 mm Hg) dose of norepinephrine into conscious rats potentiated NPY-mediated pressor responses 2-fold and also tended to increase bradycardic effect of a higher dose of NPY (by 19%). Thus hypertensive and bradycardic actions of NPY appear to depend on the level of adrenergic activity and on the interactions at the level of vascular smooth muscle, heart, and baroreceptor reflexes. During a hyperadrenergic state such as stress, cardiovascular effects of NPY may be greatly accentuated. NPY may enhance and prolong the stressinduced hypertensive responses while antagonizing adrenergic cardiostimulation.     

Haemodynamic actions of clonidine in tetraplegia--effects at rest and during urinary bladder stimulation

We studied the haemodynamic effects of clonidine (2 micrograms/kg/iv) in 7 tetraplegics and 7 normal subjects. Measurements of blood pressure, stroke volume, cardiac output and digital (finger) skin blood flow were made before and after clonidine for 60 minutes. Blood pressure, stroke volume and cardiac output did not fall in tetraplegics, unlike normals. Resting digital skin blood flow was higher in tetraplegics and fell after clonidine. In normal subjects however, an increase in digital skin blood flow occurred after clonidine. The pressor and digital vasoconstrictor responses to bladder stimulation were attenuated after clonidine. The inability of clonidine to induce a fall in blood pressure, stroke volume, cardiac output and cause peripheral vasodilation in tetraplegics is consistent with its central sympatholytic effects. Attenuation of the responses to bladder stimulation suggest an effect on spinal sympathetic neurones.     

Sensitization to pressor effects by repeated central injections of vasopressin in conscious rats

Arginine vasopressin (AVP) injected intracerebroventricularly (i.c.v.) in the nanogram range elicits increases in mean arterial blood pressure (MAP), heart rate (HR) and efferent sympathetic nerve activity (SpNA) via central V1 AVP receptor stimulation. In this study in conscious rats we investigated, whether the cardiovascular and sympathetic responses can be augmented by repeated central applications of AVP, as has been previously shown for the convulsive responses to higher i.c.v. doses of the peptide. The AVP-induced pressor (0.1 and 1.0 ng) and the SpNA (0.1 ng) responses were significantly enhanced by a second AVP challenge 24 h after the first injection. With higher doses of the peptide (3 ng), the blood pressure responses were not different between two subsequent injections, but barrel rotation occurred in 21% of the animals upon the second challenge. The pressor responses to a threshold i.c.v. dose of 1 ng angiotensin II (ANG II) were not enhanced upon a second ANG II challenge. Our results demonstrate that AVP, unlike ANG II, can sensitize central mechanisms leading to increased MAP and SpNA responses.     

Hemodynamic effects of endothelin after systemic and central nervous system administration in the conscious rat

The effects of endothelin-1 (ET-1) administered i.v. or intracerebroventricularly (i.c.v.) on arterial pressure (MAP), heart rate and cardiac output were studied in the conscious rat. Systemic injection of ET-1 (0.1 to 1 nmol/kg i.v.) increased dose-dependently MAP and decreased heart rate. The doses of 0.3 and 1 nmol/kg produced initially transient hypotension and tachycardia which were accompanied by a decrease in total peripheral resistance index (TPRI). Cardiac output was significantly reduced and TPRI increased during the pressor response to 0.3 and 1 nmol/kg ET-1. ET-1 i.c.v. (30 pmol/kg) produced a profound pressor and vasoconstrictor response which was followed by cardiovascular collapse and death within 20 min after i.c.v. injection. Low doses (1 to 10 pmol/kg) of ET-1 i.c.v. had no effect on the cardiovascular system. The present data are in accordance with the studies demonstrating biphasic blood pressure and heart rate responses to i.v. ET-1 in the rat. Profound cardiac depressor and peripheral vasoconstrictor responses were found to accompany the pressor phase. Our results also showed for the first time direct central pressor and vasoconstrictor effects of ET-1 insinuating that endothelin might be a neuropeptide participating in the central cardiovascular control.     

Central impairment of renal nerve response to stimulation of medullary pressor area in rabbit endotoxic hypotension

The present study was designed to determine if there is a central abnormality in the sympathetic efferent outflow through the brainstem in endotoxic hypotension. Mean blood pressure (MBP), heart rate (HR) and renal nerve activity (NA) were recorded simultaneously following intravenous injection of endotoxin (1 mg/kg). MBP fell significantly so that 30 min and 60 min after the injection, MBP were 76 +/- 11 mm Hg and 56 +/- 10 mm Hg respectively. Simultaneously with decreases in MBP, NA and HR also decreased significantly. Peak responses in MBP and NA to repetitive stimulation of medullary pressor area (MPA) were attenuated significantly after endotoxin. Onset and peak latencies of renal nerve discharges (RNDe) evoked by the electrical stimulation of the MPA at 5 min after endotoxin were significantly shorter than that before endotoxin, followed by a recovery to the pre-endotoxin level. Peak and total activities of RNDe were reduced significantly so that 30 min after endotoxin activities were 53 +/- 9% and 53 +/- 11% of pre-endotoxin levels respectively. However, responses in MBP, NA and RNDe to the stimulation of the thoracic sympathetic chain did not differ significantly between before and after injection of endotoxin. These data confirm the presence of a central neural abnormality in central sympathetic outflow in the hypotension induced by E. coli endotoxin.     

Defective cardiovascular reflexes and supersensitivity to sympathomimetic drugs in autonomic failure.

In 10 patients with chronic autonomic failure the clinical features and cardiovascular reflexes were correlated with the pressor responses to intravenous noradrenaline and tyramine. In all patients there was an exaggerated response to noradrenaline but a normal or only mildly exaggerated response to tyramine. Patients with lack of sinus arrhythmia and by implication baroreceptor reflex loss had greater responsiveness to pressor drugs than patients with preservation of this reflex. The responses to tyramine infusions imply that there must be sufficient noradrenaline released at defective sympathetic endings for a pressor response to occur. However, the lack of rise of plasma noradrenaline following tyramine, except in the patients with pure autonomic failure, clearly separates these responses from those of normal subjects. These results can be explained by the presence of lesions of both central and peripheral sympathetic pathways in patients with chronic autonomic failure and multiple system atrophy or Parkinsonism. The peripheral lesion, which is incomplete, may consist of replication of the receptors so causing supersensitivity with a duration of response that is little prolonged. The peripheral defect in the two patients with pure autonomic failure was found to be more complex and the prolonged response in one of these patients suggests the possibility of defective re-uptake or metabolism of noradrenaline. Clearly further study of the defects of sympathetic endings is required, including the use of other techniques such as catecholamine fluorescence. The extreme supersensitive responses underline the need for blood pressure monitoring during pressor drug studies prior to treatment, if the hazards of recumbent hypertension are to be avoided.     

Pressor and tachycardic responses evoked by microinjections of L-glutamate into the medial prefrontal cortex of unanaesthetized rats

The ventral medial prefrontal cortex (vMPFC) is involved in central cardiovascular control. In the present study, we studied the cardiovascular effects of injections of L-glutamate into the vMPFC of unanaesthetized rats and the mechanisms of these effects. Male Wistar rats were used and L-glutamate was microinjected in the vMPFC in a final volume of 200 nL. Microinjections of L-glutamate (9, 27, 81, 150 or 300 nmol) caused long-lasting, dose-related pressor and tachycardic responses in unanaesthetized rats. No differences were observed among cardiovascular responses when L-glutamate was injected into the three sub-areas that comprise the vMPFC, namely the prelimbic, the infralimbic and the dorsal peduncular cortices. No responses were observed when the dose of 81 nmol of L-glutamate was microinjected into surrounding structures such as the cingulate cortex area 1, the corpus callosum and the tenia tecta, indicating a predominant action on the vMPFC. The cardiovascular response to L-glutamate into the vMPFC was blocked by intravenous pretreatment with the ganglion blocker pentolinium (10 mg/kg, i.v.) or the beta1-adrenoceptor antagonist atenolol (1.5 mg/kg, i.v.), supporting the involvement of the cardiac sympathetic nervous system in the response to L-glutamate. Pretreatment with the muscarinic antagonist homatropine methyl bromide (1 mg/kg, i.v.) reduced the latency to the onset of the pressor and tachycardic responses to L-glutamate injected into the vMPFC without significant effects on response duration or maximum effect. We conclude that stimulation of the vMPFC with L-glutamate caused pressor and tachycardic responses in unanaesthetized rats, responses which were dependent on cardiac sympathetic nerve activation and were potentiated by blockade of peripheral muscarinic receptors.     

Motilin effects on the heart and blood vessels of the pithed rat

Motilin, a 22 amino acid polypeptide was shown to affect smooth muscle tone in the gastrointestinal tract. However, its widespread distribution in peripheral and central components of the autonomic nervous system suggest a role in other functions such as regulation of vascular tone and hemodynamic variables. Therefore, the effect of motilin on vascular tone, cardiac rhythm and blood vessel response to pressor stimuli was studied in the pithed rat. It is shown that motilin produces a prolonged depressor effect. The depressor responses were dose dependent at the range of 30 - 300 nmol/kg (max. decrease: -22 +/- 4 mmHg). In addition, motilin attenuated pressor responses to vasopressin, leukotriene D4, and the pressor effect evoked by complete spinal cord stimulation. Motilin did not affect the basal heart rate nor did it alter sympathetically induced heart rate acceleration. Motilin did not affect the circulatory level of norepinephrine or epinephrine at resting state or of norepinephrine released by spinal cord stimulation; motilin significantly suppressed epinephrine released by spinal cord stimulation. These data suggest a role for motilin in regulation of blood vessel tone by direct action on the vascular smooth muscle. In addition, motilin might play a role in regulation of epinephrine release from the adrenal medulla.     

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.     

Cardiorespiratory reflexes in mice

The various transgenic strains of mice make this species an attractive experimental model. We compared qualitatively some cardiorespiratory reflexes in two different preparations of mouse: in vivo urethane anaesthetised and a working heart-brainstem preparation (WHBP). Cardiorespiratory reflexes were evoked by stimulating baroreceptors, pulmonary vagal C fibres and cardiac receptors in both preparations, while peripheral chemoreceptors were also stimulated in the WHBP. In anaesthetised mice, activation of baroreceptors, pulmonary C fibres and cardiac receptors evoked an atropine-sensitive bradycardia (range: 21–414 bts/min) and depressed ventilation. A reflex fall in arterial pressure was also observed during pulmonary C fibre and cardiac receptor stimulation. Similar reflex bradycardia (range 81–164 bts/min) and respiratory responses were observed in the WHBP following stimulation of baro-, pulmonary C fibre and cardiac receptors. Additionally, sodium cyanide stimulation of peripheral chemoreceptors in the WHBP produced an atropine-sensitive bradycardia and increased respiratory frequency and amplitude. Thus, the cardiorespiratory reflex responses elicited in the mouse are similar to those reported in other species. It is concluded that the qualitatively similar reflex performances between the in vivo anaesthetised mouse and the WHBP make the latter an adequate model for studying central mechanisms controlling the cardiorespiratory system.     

Role of central tachykinin peptides in cardiovascular regulation in rats.

The mechanisms of action of tachykinin peptides thought to be involved in central cardiovascular regulation were examined. Intracerebroventricular injections (i.c.v.) of tachykinin peptides caused dose-dependent increases in blood pressure and heart rate. The pressor responses to substance P (SP) (10 micrograms, i.c.v.) and neurokinin A (NKA) (10 micrograms, i.c.v.) were blocked by peripheral administration of pentolinium or phentolamine, and partially attenuated by adrenalectomy. In contrast, the only initial pressor response to the neurokinin B (NKB) analogue senktide (10 micrograms, i.c.v.) was blocked by pentolinium or phentolamine. The pressor response to senktide was inhibited by pretreatment with a vasopressin V1 receptor antagonist (d(CH2)5OMe(Tyr)AVP) (10 micrograms/kg, i.v.), and senktide (10 micrograms, i.c.v.) caused an increase in plasma vasopressin level. However, the vasopressin antagonist did not influence the SP- and NKA-induced pressor responses. These results suggest that central SP and NKA increase the blood pressure and heart rate via sympathetic nerve activity, whereas central NKB increases the blood pressure mainly via release of vasopressin from the hypothalamus.