Reduction in baroreflex cardiovascular responses due to venous infusion in the rabbit.
We studied reflex bradycardia and depression of mean arterial blood pressure (MAP) during left aortic nerve (LAN) stimulation before and after volume infusion in the anesthetized rabbit. Step increases in mean right atrial pressure (MRAP) to 10 mm Hg did not result in a significant change in heart rate or MAP. After volume loading, responses to LAN stimulation were not as great and the degree of attenuation was propoetional to the level of increased MRAP. A change in responsiveness was observed after elevation of MRAP by only 1 mm Hg, corresponding to less than a 10% increase in average calculated blood volume. after an increase in MRAP of 10 mm Hg, peak responses were attenuated by 44% (heart rate) and 52% (MAP), and the initial slopes (rate of change) were reduced by 46% (heart rate) and 66% (MAP). Comparison of the responses after infusion with blood and dextran solutions indicated that hemodilution was an unlikely explanation for the attenuation of the reflex responses. Total arterial baroreceptor denervation (ABD) abolished the volume-related attenuation was still present following bilateral aortic nerve section or vagotomy. It thus appears that the carotid sinus responds to changes inblood volume and influences the reflex cardiovascular responses to afferent stimulation of the LAN. On the other hand, cardiopulmonary receptors subserved by vagal afferents do not appear to be involved. (+info)
The posterior nasal nerve plays an important role on cardiopulmonary reflexes to nasal application of capsaicin, distilled water and l-menthol in anesthetized dogs.
The sensory innervation of the cardiopulmonary reflexes to nasal application of capsaicin (CAPS), distilled water (DW) and l-menthol (LM) was studied in anesthetized dogs breathing through tracheostomy. A marked cardiopulmonary reflex was observed by CAPS and DW into the nasal cavity, while a prolongation of expiration was induced by LM. All these reflexes were significantly decreased by bilateral section of the posterior nasal nerve (PNN) and completely abolished by topical nasal anesthesia with lidocaine. Responses of the whole nerve activity of the PNN to these substances corresponded to the magnitude of the reflexes. These results indicate that PNN afferents play an important role on the reflex elicitation of the noxious, water and cold stimuli from the nasal cavity. (+info)
Neuronal activity in somatosensory cortex of monkeys using a precision grip. III. Responses to altered friction perturbations.
The purpose of this investigation was to examine the activity changes in single units of the somatosensory cortex in response to lubricating and adhesive coatings applied to a hand-held object. Three monkeys were trained to grasp an object between the thumb and index fingers and to lift and hold it stationary within a narrow position window for 1 s before release. Grip forces normal to the skin surface, load forces tangential to the skin surface, and the displacement of the object were measured on each trial. Adhesive (rosin) and lubricant (petroleum jelly) coatings were applied to the smooth metal surface of the object to alter the friction against the skin. In addition, neuronal activity evoked by force pulse-perturbations generating shear forces and slip on the skin were compared with the patterns of activity elicited by grasping and lifting the coated surfaces. Following changes in surface coatings, both monkeys modulated the rate at which grip forces normal to the skin surface and load forces tangential to the skin surface were applied during the lifting phase of the task. As a result, the ratio of the rates of change of the two forces was proportionately scaled to the surface coating properties with the more slippery surfaces, having higher ratios. This precise control of normal and tangential forces enabled the monkeys to generate adequate grip forces and prevent slip of the object. From a total of 386 single neurons recorded in the hand area of the somatosensory cortex, 92 were tested with at least 1 coating. Cell discharge changed significantly with changes in surface coating in 62 (67%) of these cells. Of these coating-related cells, 51 were tested with both an adhesive and lubricating coating, and 45 showed significant differences in activity between the untreated metal surface and either the lubricant or the adhesive coating. These cells were divided into three main groups on the basis of their response patterns. In the first group (group A), the peak discharge increased significantly when the grasped surface was covered with lubricant. These cells appeared to be selectively sensitive to slip of the object on the skin. The second group (group B) was less activated by the adhesive surface compared with either the untreated metal or the lubricated surface, and they responded mainly to variations in the force normal to the skin surface. These cells provide useful feedback for the control of grip force. The third group (group C) responded to both slips and to changes in forces tangential to the skin. Most of these cells responded with a biphasic pattern reflecting the bidirectional changes in load force as the object was first accelerated and then decelerated. One hundred sixty-eight of the 386 isolated neurons were tested with brief perturbations during the task. Of these, 147 (88%) responded to the perturbation with a significant change in activity. In most of the cells, the response to the perturbation was shorter than 100 ms with a mean latency of 44.1 +/- 16.3 (SD) ms. For each of the cell groups, the activity patterns triggered by the perturbations were consistent with the activity patterns generated during the grasping and lifting of the coated object. (+info)
Mechanisms of capsaicin- and lactic acid-induced bronchoconstriction in the newborn dog.
1. Capsaicin activation of the pulmonary C fibre vanilloid receptor (VR1) evokes the pulmonary chemoreflex and reflex bronchoconstriction. Among potential endogenous ligands of C fibre afferents, lactic acid has been suggested as a promising candidate. We tested the hypotheses that (a) lactic acid behaves as a stimulant of C fibre receptors in the newborn dog to cause reflex bronchoconstriction, and (b) lactic acid causes reflex bronchoconstriction via the same pulmonary C fibre receptor mechanism as capsaicin using the competitive capsaicin/VR1 receptor antagonist capsazepine. 2. Right heart injection of lactic acid caused a significant increase (47 +/- 8.0 %) in lung resistance (RL) that was atropine sensitive (reduced by 75 %; P < 0.05), consistent with reflex activation of muscarinic efferents by stimulation of C fibre afferents. 3. Infusion of the competitive capsaicin antagonist capsazepine caused an 80 % reduction (P < 0.01) in the control bronchoconstrictor response (41 +/- 8.5 % increase in RL) to right heart injections of capsaicin. The effects of capsazepine are consistent with reversible blockade of the VR1 receptor to abolish C fibre-mediated reflex bronchoconstriction. 4. Lactic acid-evoked increases in RL were unaffected by VR1 blockade with capsazepine, consistent with a separate lactic acid-induced reflex mechanism. 5. We conclude that (a) putative stimulation of C fibres with lactic acid causes reflex bronchoconstriction in the newborn dog, (b) capsazepine reversibly antagonizes reflex bronchoconstriction elicited by right heart injection of capsaicin, presumably by attenuating capsaicin-induced activation of the C fibre 'capsaicin' receptor (VR1), and (c) capsazepine resistance of lactic acid-induced bronchoconstriction indicates that lactic acid evokes reflex bronchoconstriction by a separate mechanism, possibly via the acid-sensing ionic channel. (+info)
Modulation of the thermoregulatory sweating response to mild hyperthermia during activation of the muscle metaboreflex in humans.
1. To investigate the effect of the muscle metaboreflex on the thermoregulatory sweating response in humans, eight healthy male subjects performed sustained isometric handgrip exercise in an environmental chamber (35 C and 50 % relative humidity) at 30 or 45 % maximal voluntary contraction (MVC), at the end of which the blood circulation to the forearm was occluded for 120 s. The environmental conditions were such as to produce sweating by increase in skin temperature without a marked change in oesophageal temperature. 2. During circulatory occlusion after handgrip exercise at 30 % MVC for 120 s or at 45 % MVC for 60 s, the sweating rate (SR) on the chest and forearm (hairy regions), and the mean arterial blood pressure were significantly above baseline values (P < 0.05). There were no changes from baseline values in the oesophageal temperature, mean skin temperature, or SR on the palm (hairless regions). 3. During the occlusion after handgrip exercise at 30 % MVC for 60 s and during the occlusion alone, none of the measured parameters differed from baseline values. 4. It is concluded that, under mildly hyperthermic conditions, the thermoregulatory sweating response on the hairy regions is modulated by afferent signals from muscle metaboreceptors. (+info)
Mechanisms involved in the metabotropic glutamate receptor-enhancement of NMDA-mediated motoneurone responses in frog spinal cord.
1. The metabotropic glutamate receptor (mGluR) agonist trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD) (10-100 microM) depolarized isolated frog spinal cord motoneurones, a process sensitive to kynurenate (1.0 mM) and tetrodotoxin (TTX) (0.783 microM). 2. In the presence of NMDA open channel blockers [Mg2+; (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK801); 3,5-dimethyl-1-adamantanamine hydrochloride (memantine)] and TTX, trans-ACPD significantly potentiated NMDA-induced motoneurone depolarizations, but not alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA)- or kainate-induced depolarizations. 3. NMDA potentiation was blocked by (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) (240 microM), but not by alpha-methyl-(2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine (MCCG) (290 microM) or by alpha-methyl-(S)-2-amino-4-phosphonobutyrate (L-MAP4) (250 microM), and was mimicked by 3,5-dihydroxyphenylglycine (DHPG) (30 microM), but not by L(+)-2-amino-4-phosphonobutyrate (L-AP4) (100 microM). Therefore, trans-ACPD's facilitatory effects appear to involve group I mGluRs. 4. Potentiation was prevented by the G-protein decoupling agent pertussis toxin (3-6 ng ml(-1), 36 h preincubation). The protein kinase C inhibitors staurosporine (2.0 microM) and N-(2-aminoethyl)-5-isoquinolinesulphonamide HCI (H9) (77 microM) did not significantly reduce enhanced NMDA responses. Protein kinase C activation with phorbol-12-myristate 13-acetate (5.0 microM) had no effect. 5. Intracellular Ca2+ depletion with thapsigargin (0.1 microM) (which inhibits Ca2+/ATPase), 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetracetic acid acetyl methyl ester (BAPTA-AM) (50 microM) (which buffers elevations of [Ca2+]i), and bathing spinal cords in nominally Ca2+-free medium all reduced trans-ACPD's effects. 6. The calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W7) (100 microM) and chlorpromazine (100 microM) diminished the potentiation. 7. In summary, group I mGluRs selectively facilitate NMDA-depolarization of frog motoneurones via a G-protein, a rise in [Ca2+]i from the presumed generation of phosphoinositides, binding of Ca2+ to calmodulin, and lessening of the Mg2+-produced channel block of the NMDA receptor. (+info)
Selective potentiation of peripheral chemoreflex sensitivity in obstructive sleep apnea.
BACKGROUND: The chemoreflexes are an important mechanism for regulation of both breathing and autonomic cardiovascular function. Abnormalities in chemoreflex mechanisms may be implicated in increased cardiovascular stress in patients with obstructive sleep apnea (OSA). We tested the hypothesis that chemoreflex function is altered in patients with OSA. METHODS AND RESULTS: We compared ventilatory, sympathetic, heart rate, and blood pressure responses to hypoxia, hypercapnia, and the cold pressor test in 16 untreated normotensive patients with OSA and 12 normal control subjects matched for age and body mass index. Baseline muscle sympathetic nerve activity (MSNA) was higher in the patients with OSA than in the control subjects (43+/-4 versus 21+/-3 bursts per minute; P<0. 001). During hypoxia, patients with OSA had greater increases in minute ventilation (5.8+/-0.8 versus 3.2+/-0.7 L/min; P=0.02), heart rate (10+/-1 versus 7+/-1 bpm; P=0.03), and mean arterial pressure (7+/-2 versus 0+/-2 mm Hg; P=0.001) than control subjects. Despite higher ventilation and blood pressure (both of which inhibit sympathetic activity) in OSA patients, the MSNA increase during hypoxia was similar in OSA patients and control subjects. When the sympathetic-inhibitory influence of breathing was eliminated by apnea during hypoxia, the increase in MSNA in OSA patients (106+/-20%) was greater than in control subjects (52+/-23%; P=0.04). Prolongation of R-R interval with apnea during hypoxia was also greater in OSA patients (24+/-6%) than in control subjects (7+/-5%) (P=0.04). Autonomic, ventilatory, and blood pressure responses to hypercapnia and the cold pressor test in OSA patients were not different from those observed in control subjects. CONCLUSIONS: OSA is associated with a selective potentiation of autonomic, hemodynamic, and ventilatory responses to peripheral chemoreceptor activation by hypoxia. (+info)
Trigeminal nerve ganglion stimulation-induced neurovascular reflexes in the anaesthetized cat: role of endothelin(B) receptors in carotid vasodilatation.
1. The effects of intravenous administration of endothelin (ET) receptor antagonists SB-209670 (0.001-10.0 mg kg(-1)), SB-217242, SB-234551 (0.01-10.0 mg kg(-1)) and BQ-788 (0.001-1.0 mg kg(-1)) were investigated on trigeminal nerve ganglion stimulation-induced neurovascular reflexes in the carotid vasculature of the anaesthetized cat. Comparisons were made with sumatriptan (0.003-3.0 mg kg(-1)) and alpha-CGRP8-37 (0.001-0.1 mg kg(-1)). 2. Trigeminal nerve ganglion stimulation produced frequency related increases in carotid blood flow, reductions in carotid vascular resistance and non-frequency related increases in blood pressure. Guanethidine (3 mg kg(-1), i.v.) blocked trigeminal nerve ganglion-induced increases in blood pressure but had no effect on changes in carotid flow or resistance. Maximal reductions in carotid vascular resistance was observed at 10 Hz, and this frequency was selected to investigate the effects of drugs on trigeminal nerve ganglion stimulation-induced responses in guanethidine treated cats. 3. Saline, alpha-CGRP8-37 SB-209670 and BQ-788 had little or no effect on resting haemodynamic parameters. SB-217242 (10 mg kg(-1), n=3) produced a 56% reduction in arterial blood pressure whereas SB-233451 (10 mg kg(-1), n=3) produced a 30% reduction in carotid vascular resistance. Sumatriptan produced dose-related reductions in resting carotid flow and increases (max. 104% at 0.3 mg kg(-1), n = 5) in vascular resistance. 4. SB-209670 (n=6-7), SB-217242 (n=3) and BQ-788 (n=3) produced inhibition of trigeminal nerve ganglion stimulation-induced reductions in carotid vascular resistance. Saline, SB-234551, alpha-CGRP8-37 and sumatriptan had no effect. 5. These data demonstrate ET(B) receptor blockade attenuates the vasodilator effects of trigeminal nerve ganglion stimulation in the carotid vascular bed of guanethidine pretreated anaesthetized cats. (+info)