Significant Cardiovascular Responses Research Articles

Abstract P173: Pivotal Role for the Kinin B1R in CB1 Receptor Mediated Neuroinflammation and Pressor Response

The cannabinoid receptors CB1R and CB2R are involved in blood pressure (BP) regulation and CB1R is implicated in the incidence of hypertension. CB1R is highly expressed in the brain but both receptors are also expressed in the heart. Prior research has demonstrated that CB1R mediates significant cardiovascular responses, including elevated BP, heightened plasma norepinephrine levels, and increased sympathetic nerve activity. Furthermore, the activation of the kinin B1 receptor (B1R) mediates similar effects when studied independently. However, the role of B1R in CB1R-mediated BP regulation and the associated signaling mechanisms remain unknown. In this study, we tested the hypothesis that B1R plays a pivotal role in CB1R-mediated pressor response, oxidative stress and neuroinflammation. To test this, we used both in vivo mouse models and in vitro primary hypothalamic neurons. Male C57BL/6NJ wild-type (WT) and B1R knockout mice (B1RKO) underwent surgical carotid artery and jugular vein catheterization to measure BP in conscious state. Following stabilization of BP for at least 90 minutes, the CB1R agonist WIN55,212-2 (300 ug/kg; i.v., WIN) or its vehicle was administered, and recordings continued for 45 minutes. WIN increased BP in WT mice (25±7 mmHg vs baseline), but this effect was blunted in B1RKO mice (n=3, p<0.05). Moreover, administration of WIN led to an augmentation of CB1R expression in the paraventricular nucleus of WT mice, but not in B1RKO mice, thereby indicating the involvement of B1R in CB1R signaling (p<0.05, n=3 mice/group). WT, but not B1RKO, mice treated with WIN displayed a significant increase in oxidative stress levels (p<0.05, n=3 mice/group), as indicated by dihydroethidium staining. To further confirm the role of B1R blockade on CB1R signaling, we cultured primary hypothalamic neurons, as neurons express the highest levels of CB1R in the brain. Neurons were stimulated with WIN (1 uM) both with and without a B1R selective antagonist (SSR240612, 10uM). The results indicated that WIN incubation for 24 hours increased CB1R expression, inflammation, and oxidative stress compared to vehicle treated, and these responses were abrogated by prior B1R blockade (p<0.05, n=5/group), consistent with the in vivo observations. These data provide novel evidence that B1R is implicated in CB1R-mediated proinflammatory responses and serves as a potential therapeutic target to reduce CB1R induced effects.

Effect of cold water hardening on the lipid profile, subclinical atherosclerosis, fat distribution, inflammation and other selected parameters of volunteers

Background and Aims : Short time cold water hardening (CWH) is associated with significant acute cardiovascular, metabolic and endocrinological responses. Many mostly observational studies have shown the possitive effect of one-time CWH in sport medicine and rehabilitation. There is however no available study following the long-term effect of repeated CWH on atherogenesis, lipid profile and lipid particles changes, inflammation and fat distribution. This study was aimed to explore the suggested possivite effects.

Immediate physiological effects of acute electronic cigarette use in humans: A systematic review and meta-analysis

BackgroundElectronic cigarettes (e-cigs) are widely used devices that were initially created to aid in smoking cessation. However, their acute physiological effects are unclear and there have been a number of E-cig and Vaping Acute Lung Injury (EVALI) events reported. Research questionWhat are the immediate physiological effects (i.e. cardiovascular, respiratory or blood-based responses) of acute e-cig usage in humans? Study design and MethodsPubMed, Web of Science, Cochrane and Scopus databases were searched for English or French peer-reviewed articles published until May 20, 2021 and measuring at least one physiological parameter before and after using an e-cig. The study followed PRISMA guidelines and assessed article quality using the Downs and Black checklist. Independent extraction was conducted by two reviewers. Data were pooled using random-effect models. Sensitivity analysis and meta-regressions were performed to explore heterogeneity. Main outcomesSystolic and diastolic blood pressure, heart rate, augmentation index (AIx75), fraction of exhaled nitric oxide (FeNO), and spirometry were the most frequently assessed parameters and were therefore chosen for meta-analyses. ResultsOf 19823 articles screened, 45 articles were included for the qualitative synthesis, and 27 articles (919 patients) were included in meta-analyses. Acute use of nicotine e-cig was associated with increased heart rate(SMD = 0.71; 95%CI 0.46–0.95), systolic blood pressure (SMD = 0.38; 95%CI 0.18–0.57), diastolic blood pressure (SMD = 0.52; 95%CI 0.33–0.70), and augmentation index AIx75 (SMD = 0.580; 95%CI 0.220–0.941), along with decreased FeNO (SMD = −0.26; 95%CI -0.49 to −0.04). E-cig exposure wasn't associated with significant changes in any spirometry measure. InterpretationAcute use of nicotine e-cigs was associated with statistically significant cardiovascular and respiratory responses. These devices have a physiological impact that could be clinically relevant, especially in terms of cardiovascular morbidity. However, the direct consequences of long-term e-cig use needs to be further explored.

Cardiovascular Responses and Cardiac Work of Selected Daily Activities in Young Healthy Indian Participants

Background: Studies suggest that habitual daily activities may result in significant cardiovascular responses that might have implications for individuals with coronary artery disease. This study determined the cardiac work for various activities of daily living among healthy young participants. Methods: We evaluated cardiovascular responses in 42 young adults (21 male, 21 female) to graded activities. Subjects were divided into three groups. In each group, one light, one moderate, and one heavy activity were performed based on published METS. Cardiovascular responses were evaluated using impedance cardiography (BOMED Instruments, USA) and automated blood pressure monitor (Welch Allyn, USA). Cardiac work was computed as the double product (heart rate × systolic blood pressure) and triple product (systolic blood pressure × cardiac output [stroke volume × heart rate]). Perceived exertion was evaluated using Borg’s scale. Results: There was high inter-individual variability in cardiovascular responses for each activity. There were, by and large, no gender differences across the activities. Cardiac work was significantly higher with heavy activities than light activities using both indices; however, the triple product showed greater discriminatory ability in evaluating differences in cardiac work across all categories of activities. Conclusion: The data suggest a need to develop a compendium of cardiac work related to habitual activities to guide doctors and patients.

Pharmacologic attenuation of the hyperdynamic response to supraceliac aortic clamping

Aortic occlusion is accompanied by a hyperdynamic cardiovascular response secondary to increased systemic vascular resistance and increased cardiac output. This study was designed primarily to determine the safety and cardiovascular response to hydrogen sulfide (H2S; HS) administration with supraceliac aortic cross-clamp and, secondarily, on short-duration resuscitation. A validated porcine model (five sham swine compared with five controls) demonstrated a significant hyperdynamic cardiovascular response to 35% blood volume hemorrhage, 50-minute suprarenal aortic cross-clamping, and 6-hour resuscitation. Eight additional experimental swine were administered HS at 4 mg/min during aortic cross-clamping. During the cross-clamp period, hemodynamic curves of mean arterial pressure and heart rate demonstrated a blunting effect with HS administration, with a significant decrease being seen with mean arterial pressure at the end of the cross-clamp period (120 vs 149 mm Hg; P = .04). Resuscitation requirements were significantly reduced at 6 hours because the HS cohort received 8 L less crystalloid (P = .001) and 10.4 mg less epinephrine (P < .001). There was not a significant change in cardiac output, systemic vascular resistance, pulmonary vascular resistance, or pathologic liver analysis. The administration of HS during the 50 minutes of supraceliac aortic cross-clamp significantly reduced stress of the left heart. On clamp release, HS significantly reduced the need for volume and pressors. HS has positive benefits during cross-clamp and subsequent resuscitation, demonstrating that targeted pharmacologic therapy is possible to minimize adverse physiologic changes with aortic occlusion.

Blood pressure and the contractility of a human leg muscle

These studies investigate the relationships between perfusion pressure, force output and pressor responses for the contracting human tibialis anterior muscle. Eight healthy adults were studied. Changing the height of tibialis anterior relative to the heart was used to control local perfusion pressure. Electrically stimulated tetanic force output was highly sensitive to physiological variations in perfusion pressure showing a proportionate change in force output of 6.5% per 10 mmHg. This perfusion-dependent change in contractility begins within seconds and is reversible with a 53 s time constant, demonstrating a steady-state equilibrium between contractility and perfusion pressure. These stimulated contractions did not produce significant cardiovascular responses, indicating that the muscle pressor response does not play a major role in cardiovascular regulation at these workloads. Voluntary contractions at forces that would require constant motor drive if perfusion pressure had remained constant generated a central pressor response when perfusion pressure was lowered. This is consistent with a larger cortical drive being required to compensate for the lost contractility with lower perfusion pressure. The relationship between contractility and perfusion for this large postural muscle was not different from that of a small hand muscle (adductor pollicis) and it responded similarly to passive peripheral and active central changes in arterial pressure, but extended over a wider operating range of pressures. If we consider that, in a goal-oriented motor task, muscle contractility determines central motor output and the central pressor response, these results indicate that muscle would fatigue twice as fast without a pressor response. From its extent, timing and reversibility we propose a testable hypothesis that this change in contractility arises through contraction- and perfusion-dependent changes in interstitial K(+) concentration.

Stress response dysregulation and stress-induced analgesia in nicotine dependent men and women

Alterations in the stress response and endogenous pain regulation mechanisms may contribute directly and indirectly to maintenance of nicotine dependence and relapse. We examined the extent to which nicotine dependence alters endogenous pain regulatory systems, including the hypothalamic-pituitary-adrenocortical axis, cardiovascular activity, and stress-induced analgesia. Smokers and nonsmokers attended a laboratory session that included assessment of hormonal and cardiovascular responses to stress. Smokers smoked at their regular rate prior to the session. The hand cold pressor and heat thermal pain tests were completed twice, once after acute stress (public speaking and math tasks) and the other after rest. While smokers and nonsmokers exhibited significant hormonal and cardiovascular responses to stress, smokers exhibited blunted stress responses relative to nonsmokers. They also exhibited diminished stress-induced analgesia. Results demonstrate altered stress response and diminished stress-induced analgesia among chronic smokers, and suggest that these dysregulated physiological responding may contribute to altered endogenous pain regulation.

Cardiovascular effects of acetylcholine microinjection into the ventrolateral and dorsal periaqueductal gray of rats

In the present study, we describe the cardiovascular effects of local acetylcholine (Ach) microinjection into both the ventrolateral (vlPAG) and dorsal (dPAG) periaqueductal gray areas of anesthetized rats and the possible local receptors involved with these responses. Microinjection of Ach (9, 27, 45 or 81nmol/50nL) into the vlPAG caused dose-related depressor responses. These hypotensive responses were blocked by local pretreatment with increasing doses of the nonselective muscarinic antagonist atropine (1, 3 or 9nmol/50nL). The microinjection of Ach into the dPAG caused no significant cardiovascular responses in anesthetized rats. In conclusion, the present findings suggest that a cholinergic system present in the vlPAG, but not in the dPAG, is involved with cardiovascular system control. Moreover, these cardiovascular responses evoked by Ach are mediated by muscarinic receptors.

Cardiovascular and metabolic responses during isokinetic shoulder rotators strength testing in healthy subjects

Background: Although there have been many studies on isokinetic shoulder exercises in evaluation and rehabilitation programs, the cardiovascular and metabolic responses of those modes of muscle strength exercises have been poorly investigated. Objective: To analyze cardiovascular and metabolic responses during a standardized test used to study the internal (IR) and external (ER) rotators maximal isokinetic strength. Methods: Four days after an incremental exercise test on cycle ergometer, ten healthy subjects performed an isokinetic shoulder strength evaluation with cardiovascular (Heart rate, HR) and metabolic gas exchange (VO 2 ) analysis. The IR and ER isokinetic strength, measured in seated position with 45° of shoulder abduction in scapular plane, was evaluated concentrically at 60, 120 and 240°/s and eccentrically at 60°/s, for both shoulder sides. An endurance test with 30 repetitions at 240°/s was performed at the end of each shoulder side testing. Results: There was a significant increase of mean HR with isokinetic exercise (P < 0.05). Increases of HR was 42-71 % over the resting values. During endurance testing, increases of HR was 77-105% over the resting values, and corresponded to 85-86% of the maximal HR during incremental test. Increase of V0 2 during isokinetic exercises was from 6-11 ml/min/kg to 20-43 ml/min/kg. Conclusion: This study performed significant cardiovascular and metabolic responses to isokinetic exercise of rotators shoulder muscles. A warm-up should be performed before maximal high-intensity isokinetic shoulder testing. Our results indicated that observation and supervision are important during testing and/or training sessions, especially in subjects with risk for cardiovascular disorders.

Série fracionada da extensão de joelho proporciona maiores respostas cardiovasculares que séries contínuas

The strength training can promote significant cardiovascular responses during its performance and it is interesting to devise strategies to reduce them, without compromising the strength production. To compare the acute cardiovascular responses of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), heart rate (HR) and double product (DP) during the unilateral knee extension (four series of 8 maximum repetitions) performed continuously or discontinuously. Both protocols involved a 2-minute interval between the series and the discontinuous protocol had an extra interval of 2 seconds between the 4th and the 5th repetitions. Eight healthy men trained in muscular strength (aged 26+/- 6 years) participated in the data collection and were randomly divided in two non-consecutive days. The cardiovascular responses were measured by photoplethysmography (Finapres, Ohmeda, Louisville, CO, USA) at rest, at the end of each series and 2 minutes after the performance of each protocol. The discontinuous series showed significantly higher values when compared to the protocol of the continuous series for: SAP (mmHg) at the 2nd (173.1+/- 5.4 vs 152.0+/- 4.0; p=0.001), 3rd (188.9+/- 8.6 vs 162.4+/- 6.0; p=0.000) and 4th series (193.1+/- 8.1 vs 161.6+/- 5.9; p=0.000); DAP (mmHg) at the 3rd (103.8+/- 4.1 vs 86.1+/- 3.3; p=0.000) and 4th series (104.1+/- 2.7 vs 83.4+/- 3.3; p=0.000); DP (mmHg.bpm) at the 2nd (17,907.5+/- 1,350.7 vs 14,541.9+/- 1,848.0; p=0.03), 3rd (19,687.3+/- 1,444.3 vs 15,612.1+/- 1,180.3; p=0.008) and 4th series (21,271.0+/- 1,794.2 vs 15,992.0+/- 1,093.4; p=0.001). The discontinuous protocol promoted higher increase in pressure responses when compared to the continuous one. However, due to the characteristics of the study design, further studies are necessary to support these findings.

Cardiovascular Responses Elicited by Intragastric Administration of BDL and GHB

Gamma-hydroxybutyrate (GHB) and its metabolic precursor, 1,4-butanediol (BDL), are widely used recreational drugs. Although most commonly described as CNS depressants, GHB and BDL elicit significant sympathomimetic cardiovascular responses [increases in mean arterial pressure (MAP) and heart rate] when administered parenterally. Given that humans most commonly ingest both drugs orally, we examined the dose-response relationships for intragastrically administered GHB and BDL on MAP and heart rate in conscious rats using radiotelemetry. The intragastric administration of GHB increased MAP. BDL increased both MAP and heart rate and was approximately 10-fold more potent as a cardiovascular stimulant than GHB when administered intragastrically. Pretreatment with ethanol prevented the lethality of BDL. These data indicate that 1) both GHB and BDL produce cardiovascular responses when administered intragastrically and 2) BDL is more potent and potentially more dangerous than GHB when administered via this route.

Which airway should I use?

To summarize recent findings for the optimal airway device for patients in the operating room and for medical personnel with limited experience in out-of-hospital airway management. Extraglottic airway devices, like the laryngeal mask airway, are increasingly used for airway management in patients undergoing elective surgery. New devices with separate gastric access reduce the risk of aspiration, providing higher airway seal pressure and extending the range of clinical use (e.g., for patients with surgical procedures in the prone position). The major advantages are reduced airway morbidity and less significant cardiovascular responses. Extraglottic airway devices insertion is easier to learn, and the skill is better retained. Failure to secure the airway in critically ill emergency patients can drastically increase the likelihood of poor or fatal outcome. Recently published studies recommend a shift in the curriculum for medical students and other healthcare providers from conventional laryngoscopic tracheal intubation towards the use of extraglottic airway devices. The intubating laryngeal mask might play a major role because it facilitates both ventilation and tracheal intubation. Extraglottic airway devices are increasingly used for airway management not only in patients for elective surgery, but also in out-of-hospital settings, when less experienced personnel have to secure the airway.

Emotional irritation before mental stress is associated with enhanced peripheral norepinephrine

Research suggests equivocal findings on associations of catecholamines and mood. Our study investigated the associations of emotional state, blood pressure and catecholamines in 55 healthy males undergoing mental stress. We especially checked the reported link between norepinephrine (NE) and emotional irritation. Blood pressure (SBP, DBP) and heart rate (HR) were continuously monitored. NE and epinephrine (EPI) were measured before, after, and 20 minutes after stress. Participants were divided into irritated versus non-irritated and anxious versus non-anxious subjects by median split on their baseline questionnaires. The task elicited significant cardiovascular, hormonal, and psychological stress responses. NE levels were significantly correlated with irritation before stress. Irritated subjects showed significantly higher DBP and NE than non-irritated subjects. The higher NE and DBP levels in the irritated participants suggest detrimental psycho-physiological interrelations promoting the development of stress-mediated cardiovascular diseases. Heightened emotional irritation before stress may be regarded as a psychological risk factor.

Cardiovascular responses to noradrenaline microinjection in the ventrolateral periaqueductal gray of unanesthetized rats

The periaqueductal gray area (PAG) is a mesencephalic area involved in cardiovascular modulation. Noradrenaline (NA), a neurotransmitter involved in central blood pressure control, is present in the rat PAG. We report here on the cardiovascular effects caused by NA microinjection into the ventrolateral PAG (vlPAG) of unanesthetized rats and the peripheral mechanism involved in their mediation. NA microinjection in the vlPAG of unanesthetized rats evoked dose-related pressor and bradycardiac responses. No significant cardiovascular responses were observed in urethane-anesthetized rats. The pressor response was potentiated by pretreatment with the ganglion blocker pentolinium (5 or 10 mg/kg, intravenously). Pretreatment with the vasopressin antagonist dTyr(CH2)5 (Me)AVP (50 microg/kg, intravenously) blocked the pressor response evoked by the NA microinjection into the vlPAG. Additionally, circulating vasopressin content was found to be significantly increased after NA microinjection in the vlPAG. The results suggest that activation of noradrenergic synapses within the vlPAG modulates vasopressin release in unanesthetized rats.

Cardiovascular and Intravesical Pressure Responses during Natural Micturition in Conscious Rats

Urinary bladder distension is known to influence the cardiovascular system under a pathophysiological condition such as spinal cord injury, hypertension, and arteriosclerosis. A reflex due to bladder distension and/or contraction is considered as one reason for the cardiovascular disturbance associated with micturition. However, it has remained unknown how much intravesical pressure (IVP) rises during micturition in daily life and to what extent mean arterial blood pressure (MAP) and heart rate (HR) respond at that time. To answer these questions, we attempted to examine the direct changes in IVP, MAP, and HR during natural micturition in freely moving conscious rats. IVP increased from the baseline value of 4 +/- 0.2 mmHg to 14 +/- 0.5 mmHg during natural micturition. Although MAP and HR began to increase before micturition, the increases in MAP and HR became significant 1-4 s before its onset. The peak increases in MAP and HR (7 +/- 0.8 mmHg and 14 +/- 3 beats/min, respectively) were delayed by 2 s from the peak IVP. Following an administration of xylocaine into the urinary bladder, the increases in MAP and HR during micturition were significantly blunted to 5 +/- 2 mmHg and 8 +/- 3 beats/min, although IVP increased the same as it did during micturition without xylocaine. Moreover, the relationship between IVP and MAP or HR during natural micturition resembled that between IVP and the vesico-cardiovascular reflex responses during isovolumic bladder contraction in anesthetized rats. Therefore it is concluded that natural micturition in freely moving conscious rats accompanies the significant cardiovascular responses despite a limited increase in intravesical pressure, to which a reflex from the urinary bladder may substantially contribute.

Effect of mivacurium 200 and 250 &mgr;g/kg in infants during isoflurane anesthesia: a randomized controlled trial [ISRCTN07742712

BackgroundInfants usually respond differently to a neuromuscular relaxant compared to children or adults. Isoflurane is commonly used as an anesthetic gas in infants. In an RCT design, we investigated whether a dose of mivacurium 250 μg/kg results in faster onset of action than 200 μg/kg in infants under isoflurane anesthesia. Spontaneous recovery times and cardiovascular response were also evaluated.MethodsTwenty-four low surgical risk children, aged 6–24 months, undergoing an elective surgery and requiring tracheal intubation were selected. After anesthetic induction, patients randomly received an iv bolus dose of mivacurium 200 or 250 μg/kg. After maximal relaxation, the patient was intubated. Isoflurane was administered to maintain anesthetic level during the surgical procedure. Neuromuscular function was monitored by accelerometry (TOF-Guard) at the adductor pollicies. The first twitch (T) of the TOF and the T4/T1 were measured. The time-course of heart rate and systolic and diastolic blood pressure were analysed by transforming them into their respective areas under the curve.ResultsMivacurium 250 μg/kg produced a maximal T block faster than 200 μg/kg, i.e. 2.4 ± 1.1 vs. 3.5 ± 1.4 min (p < 0.05). Spontaneous recovery times were similar in both groups. Heart rate was similar between doses while systolic and diastolic blood pressures were lower with the higher dose (p < 0.05). Flushing was observed in two cases, one in each group.ConclusionsThe maximal effect of mivacurium 250 μg/kg, in infants under isoflurane anesthesia, was present one minute faster than 200 μg/kg. However, it produced a significant cardiovascular response.

Effect of Oral Antihistamine on Mivacurium-Induced Histamine Release and Side Effects

Comment: With the exception of doxacurium and cisatracurium, doses of benzoisoquinolonium derivatives commonly have been limited by drug-induced histamine release. Such histamine release could be prevented by reducing the dose of drug and by administering it in divided doses or over a prolonged period of time (such as 90 sec). Alternatively, the clinical effect of histamine release can be significantly mitigated by IV administration of H1 and H2 antagonists. The present study indicates that oral antihistamines can be used. Moreover, the authors report that subjects receiving the antihistamine actually evidenced a reduction in plasma histamine levels as well as a reduction in H1- and H2-mediated side effects. However, it also should be noted that isolated subjects still appeared to have significant cardiovascular response (e.g., more than a 20% decrease in systolic blood pressure).

Adrenomedullin microinjection into the area postrema increases blood pressure.

Adrenomedullin (ADM) circulates in the blood at concentrations comparable to other vasoactive peptides with established roles in cardiovascular regulation. Intravenously administered ADM produces a clear hypotensive effect, whereas intracerebroventricular microinjections result in increases in blood pressure (BP). Recently, we demonstrated that ADM influences neurons of the area postrema (AP), a central nervous system site implicated in cardiovascular control. However, to address directly the physiological significance of the actions of ADM at the AP, an in vivo microinjection study was undertaken. ADM, at two concentrations (1 and 10 microM), in volumes of 50, 100, and 200 nl, was microinjected into the AP or NTS of 21 urethan-anesthetized male Sprague-Dawley rats. Microinjection of 10 microM ADM (100 nl) resulted in significant transient (2-5 min) increases in BP [120 s area under the curve (AUC): 684.3 +/- 268.6 mmHg/s (P < 0.05)], and heart rate (HR) [AUC: 12.5 +/- 4.5 beats/min (P < 0.05)]. The lower concentration of ADM (1 microM) had no effect on either BP (179.1 +/- 143.6 mmHg/s) or HR (0.8 +/- 2.6 beats/min). ADM was also microinjected into the immediately adjacent nucleus of the solitary tract, where it was found to be without effect on either BP or HR. This study demonstrates, for the first time, a physiological role for ADM acting at a specific brain site, the AP, to produce significant cardiovascular responses.

The myth of nitric oxide in central cardiovascular control by the nucleus tractus solitarii.

Considerable evidence suggests that nitroxidergic mechanisms in the nucleus tractus solitarii (NTS) participate in cardiovascular reflex control. Much of that evidence, being based on responses to nitric oxide precursors or inhibitors of nitric oxide synthesis, has been indirect and circumstantial. We sought to directly determine cardiovascular responses to nitric oxide donors microinjected into the NTS and to determine if traditional receptor mechanisms might account for responses to certain of these donors in the central nervous system. Anesthetized adult Sprague Dawley rats that were instrumented for recording arterial pressure and heart rate were used in the physiological studies. Microinjection of nitric oxide itself into the NTS did not produce any cardiovascular responses and injection of sodium nitroprusside elicited minimal depressor responses. The S-nitrosothiols, S-nitrosoglutathione (GSNO), S-nitrosoacetylpenicillamine (SNAP), and S-nitroso-D-cysteine (D-SNC) produced no significant cardiovascular responses while injection of S-nitroso-L-cysteine (L-SNC) elicited brisk, dose-dependent depressor and bradycardic responses. In contrast, injection of glyceryl trinitrate elicited minimal pressor responses without associated changes in heart rate. It is unlikely that the responses to L-SNC were dependent on release of nitric oxide in that 1) the responses were not affected by injection of oxyhemoglobin or an inhibitor of nitric oxide synthesis prior to injection of L-SNC and 2) L- and D-SNC released identical amounts of nitric oxide when exposed to brain tissue homogenates. Although GSNO did not independently affect blood pressure, its injection attenuated responses to subsequent injection of L-SNC. Furthermore, radioligand binding studies suggested that in rat brain synaptosomes there is a saturable binding site for GSNO that is displaced from that site by L-SNC. The studies suggest that S-nitrosocysteine, not nitric oxide, may be an interneuronal messenger for cardiovascular neurons in the NTS.

Increased nerve growth factor inducible-A gene and c-fos messenger RNA levels in the rat midbrain and hindbrain associated with the cardiovascular response to electrical stimulation of the mesencephalic cuneiform nucleus

Functional neuronal connections associated with the cardiovascular response to unilateral low-intensity electrical stimulation of the mesencephalic cuneiform nucleus were examined in the halothane-anaesthetized and paralysed rat by in situ hybridization histochemistry using specific 35S-labelled oligonucleotides for detection of nerve growth factor inducible-A gene (NGFI-A) and c-fos messenger RNAs. Stimulation of the cuneiform nucleus increased mean arterial pressure and heart rate by 20 +/- 0.5 mmHg and 35 +/- 3 b.p.m., respectively, while no significant cardiovascular response was observed in animals stimulated in the inferior colliculus or in sham-operated animals. Cuneiform nucleus stimulation produced increased NGFI-A and c-fos messenger RNA levels in the Kölliker-Fuse and parabrachial nuclei ipsilaterally, and the cuneiform nucleus, dorsal periaqueductal gray and caudal ventrolateral medulla bilaterally at levels significantly greater than those in inferior colliculus-stimulated, sham-operated and naive, unoperated animals. NGFI-A, but not c-fos, messenger RNA expression was increased bilaterally in the caudal portion of the nucleus of the solitary tract and inferior olive. These results are consistent with previous neuroanatomical tract-tracing studies of afferent and efferent pathways from the cuneiform nucleus and indicate that these midbrain and hindbrain structures may be involved in the pressor and tachycardic responses associated with stimulation of the cuneiform nucleus. The ipsilateral nature of responses in certain brain areas may be explained by the absence of decussating pathways and/or the presence of multisynaptic connections which attenuate bilateral signal transmission. Characterization of these activated neuronal structures using other compatible labelling techniques should further elucidate the mechanisms by which these central nervous system structures are integrated in the cardiovascular responses to stimulation of the cuneiform nucleus.