Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CONSCIOUSNESS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources

Consciousness, reduction, and emergence. Some remarks.

Consciousness is often seen as requiring a special kind of explanation. But the various aspects of self-awareness can presumably emerge when certain levels of complexity are reached in an organism: it is not necessary to assume additional mechanisms or hidden causes. Looking at the most fundamental level, that of elementary particle physics, three principles appear--the conformability of nature to herself, the applicability of the criterion of simplicity, and the utility of certain parts of mathematics in describing physical reality--which are in themselves emergent properties of the fundamental laws of physics. At successive levels, it is the availability of similar mathematical descriptions from related problems that makes the next step appear with simplicity and elegance. Thus, once the concept of emergence is properly established, a huge burden is lifted from the inquiring mind. The whole explanatory loop may be closed by looking at the ability of the human mind to figure out the laws of nature. All the other sciences emerge in principle from fundamental physics plus historical accidents, even though "reduction" is obviously inadequate as a strategy. While bridges or staircases are under construction connecting the various sciences, each science needs to be studied at its own level as well. Although the idea of "vital forces" in biology alien to physics and chemistry has largely disappeared, consciousness remains the last refuge of obscurantists. Finally, it is argued that appeals to the alleged weirdness of quantum mechanics are based on a misunderstanding and are unlikely to have any place in a discussion of consciousness.

Animals↗

Identification of arterial wall dynamics in conscious dogs.

Viscoelastic properties determine the dynamic behaviour of the arterial wall under pulsatile pressure and flow, suggesting time- or frequency-dependent responses to changes in wall stress and strain. The objectives of the present study were: (i) to develop a simplified model to derive simultaneously the elastic, viscous and inertial wall moduli; (ii) to assess Young's modulus as a function of frequency, in conscious, chronically instrumented dogs. Parametric discrete time models were used to characterise the dynamics of the arterial system based on thoracic aortic pressure (microtransducer) and diameter (sonomicrometry) measurements in control steady state and during activation of smooth muscle with the alpha-adrenoceptor agonist phenylephrine (5 microg kg(-1) min(-1), I.V.), in eight conscious dogs. The linear autoregressive model and a physically motivated non-linear model were fitted to the input-output (stress-strain) relationship. The aortic buffering function (complex Young's modulus) was obtained in vivo from the identified linear model. Elastic, viscous and inertial moduli were significantly increased from control state ((44.5 +/- 7.7) x 10(4) Pa; (12.3 +/- 4.7) x 10(4) Pa s; (0.048 +/- 0.028) x 10(4) Pa s(2) ) to active state ((85.3 +/- 29.5) x 10(4) Pa, P < 0.001; (22.4 +/- 8.3) x 10(4) Pa s, P < 0.05; (0.148 +/- 0.060) x 10(4) Pa s(2), P < 0.05). These moduli, obtained using the linear model, did not present significant differences compared with those derived using the non-linear model. In control conditions, the magnitude of the normalised complex Young's modulus was found to be similar to that reported in previous animal studies ranging from 1 to 10 Hz. During vascular smooth muscle activation, this modulus was found to be increased with regard to control conditions (P < 0.01) in the frequency range used in this study. The frequency-dependent Young's modulus of the aortic wall was obtained for the first time in conscious, unsedated dogs. The parametric modelling approach allows us to verify that vascular smooth muscle activation increases the elastic, viscous and inertial moduli with the advantage of being able to track their time evolution. Furthermore, under activation, the aortic wall remains stiff in the physiological frequency range, suggesting the impairment of the arterial buffering function. Experimental Physiology (2001) 86.4, 519-528.

Animals↗

The central release of acetylcholine during consciousness and after brain lesions.

1. Acetylcholine (ACh) has been collected from the visual cortex of anaesthetized rabbits during stimulation of the lateral geniculate body and after cutting central nervous pathways. ACh has also been collected from the visual cortex of conscious, free-moving rabbits.2. After a unilateral ;vertical' lesion separating the geniculate body from more centrally situated nuclei, ACh release evoked from the contralateral cortex by geniculate body stimulation was abolished but evoked release from the ipsilateral cortex was only reduced.3. After a bilateral, ;horizontal' lesion separating the thalamic nuclei from the reticular formation, unilateral geniculate stimulation gave an increased ACh release from the ipsilateral but not from the contralateral visual cortex.4. The ;vertical' and ;horizontal' lesions had no permanent effect on the spontaneous release of ACh from the visual cortex.5. Unilateral destruction of the geniculate body reduced the spontaneous release of ACh from the ipsilateral cortex but did not affect the contralateral release.6. The spontaneous and directly evoked ACh release from chronically undercut areas of cortex was found to be considerably lower than from intact areas of cortex.7. A high output of ACh was obtained from the visual cortex of conscious, free-moving rabbits. The rate of ACh release was closely related to the activity and state of arousal of the animals.8. These results support an earlier suggestion that two major ascending cholinergic systems exist in the rabbit brain. One pathway is the non-specific reticulo-cortical tract responsible for cortical arousal and the other is the more specific thalamo-cortical pathway associated with augmenting and repetitive after-discharge responses. The functional significance of these two cholinergic pathways and their role in the conscious animal are discussed.

Acetylcholine↗

Increasing atrial pressure during cardiac tamponade does not elevate plasma levels of the peptide ANP in conscious dogs.

1. Factors influencing the release of atrial natriuretic peptide (ANP) are not well understood. We chose a conscious euvolaemic canine model of cardiac tamponade to investigate the roles played by atrial blood pressure, transmural atrial pressure, atrial size, and arginine vasopressin (AVP) on ANP release since during cardiac tamponade the atrial transmural pressure and size decrease as atrial pressure increases. The haemodynamic response to acute cardiac tamponade in conscious dogs differs from that in anaesthetized or convalescent animals. 2. Eighteen mongrel dogs were prepared for the chronic measurement of: ascending aortic blood flow (electromagnetic flowmeter); intrapericardial, right atrial and aortic blood pressures, and the evaluation of right atrial size (two-dimensional echocardiography). After the animals had recovered from surgery, data were collected during progressive cardiac tamponade induced by intrapericardial infusion of warmed saline (20 ml/min) to the point of haemodynamic decompensation. Decompensated cardiac tamponade (DCT) was defined as a decline in mean aortic blood pressure to 70% of the level present when the pericardial space was drained of fluid (baseline) and was produced in all animals within 25 min. Plasma ANP and AVP levels were measured at selected intervals. 3. Cardiac output decreased progressively as intrapericardial pressure, right atrial blood pressure and heart rate increased. Mean aortic blood pressure was well maintained until late in tamponade when it declined rapidly, while atrial transmural pressure and atrial size decreased continuously. These haemodynamic changes were associated with stable ANP plasma levels. There was no significant change in AVP plasma levels from the baseline level of 2.5 +/- 0.4 pg/ml until the point of DCT when they abruptly increased to 117 +/- 36.4 pg/ml. 4. The ability to increase ANP plasma levels was confirmed in a subgroup of animals by noting the response to AVP injection. Although the animals were able to increase plasma ANP levels in response to AVP injection (when intrapericardial pressure was normal) and the plasma AVP level was markedly increased late in tamponade, the time course of plasma AVP elevation could not explain why plasma ANP levels did not decrease as atrial transmural pressure and atrial size declined. 5. Thus, although atrial distention and not simply atrial blood pressure must play a dominant role in stimulating ANP release from the atria, decreased atrial size does not result in lowering of plasma ANP levels below baseline levels in this conscious euvolaemic canine model.

Animals↗

Mesenteric blood pressure profile of conscious, freely moving rats.

1. Blood pressure has been measured in the aorta and at four points in the mesenteric circulation of conscious, freely moving rats under physiological, resting conditions. 2. Using small polythene catheters, blood pressure was measured simultaneously in the aorta and either distally in the superior mesenteric artery (group A), at the base of a mesenteric arterial arcade (vessel diameter ca 100 microns) (group B), at the base of a mesenteric venous arcade (group C) or distally in the superior mesenteric vein (group D). Local blood flow distribution proximal and distal to the measurement point was restored after the cannulations through appropriate ligations. 3. In conscious animals 5-17 h after surgery, systemic mean blood pressure was 121 +/- 2 mmHg. Local pressures at the four locations (as a percentage of systemic pressure) were: 95 +/- 1% in group A, 64 +/- 2% in group B, 13 +/- 1% in group C and 7 +/- 1% in group D. Thus, large arteries dissipated 5% of the total pressure drop, arcade small arteries 31%, the intramural circulation 51%, arcade veins 6% and the remaining veins plus the hepatic circulation 7%. 4. Immediately after surgery, the corresponding pressure drops were 4, 16, 66, 5 and 9%, respectively, thus emphasizing that the pressure profile can be profoundly affected by surgery and anaesthesia. 5. The data indicate that under resting conditions in conscious, freely moving rats, half the mesenteric vascular resistance resides outside the intramural circulation, primarily in the arcade small arteries.

Animals↗

Consciousness and complexity.

Conventional approaches to understanding consciousness are generally concerned with the contribution of specific brain areas or groups of neurons. By contrast, it is considered here what kinds of neural processes can account for key properties of conscious experience. Applying measures of neural integration and complexity, together with an analysis of extensive neurological data, leads to a testable proposal-the dynamic core hypothesis-about the properties of the neural substrate of consciousness.

Animals↗

Recovery of consciousness after epileptic seizures in children.

OBJECTIVE: To investigate the duration of postictal impairment of consciousness and the factors that affect it. PATIENTS AND METHODS: 90 children aged 1-16 years (37 male, 53 female, median age 6 years), attending the accident and emergency department, and inpatients of Leeds General Infirmary, Leeds, UK, who had experienced seizures involving impairment of consciousness. Interventions-hourly modified paediatric coma scores were determined, until a coma score of 15 was obtained. Linear regression analysis was used to determine the factors influencing recovery time. RESULTS: 49 children were excluded owing to incomplete coma scoring, lost notes and refusal of consent. Median time for full recovery of consciousness was 38 min (0.63 h, range 0.05-17 h). Median recovery time was 18 min (0.3 h, range 0.05-9 h) from febrile seizures, which was significantly shorter than for seizures of other aetiologies (p<0.05), 1.35 h (range 0.07-13.13 h) from idiopathic seizures, 1.25 h (0.07-12.1 h) from remote symptomatic seizures and 4.57 h (0.25-17 h) from acute symptomatic seizures. Median recovery time after the use of benzodiazepines was 3.46 h (range 0.08-14.25 h), and was significantly longer (p<0.05) than for seizures not treated with benzodiazepines (median 0.47 h, range 0.05-17 h). Age, sex, seizure type and duration did not significantly affect recovery time. CONCLUSIONS: Most children experiencing febrile seizures recover within 30 min. An acute symptomatic aetiology should be considered if recovery takes >1 h.

Adolescent↗

Relationship between regional cerebral metabolism and consciousness disturbance in traumatic diffuse brain injury without large focal lesions: an FDG-PET study with statistical parametric mapping analysis.

BACKGROUND: The cerebral metabolism of patients in the chronic stage of traumatic diffuse brain injury (TDBI) has not been fully investigated. AIM: To study the relationship between regional cerebral metabolism (rCM) and consciousness disturbance in patients with TDBI. METHODS: 52 patients with TDBI in the chronic stage without large focal lesions were enrolled, and rCM was evaluated by fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) with statistical parametric mapping (SPM). All the patients were found to have disturbed consciousness or cognitive function and were divided into the following three groups: group A (n = 22), patients in a state with higher brain dysfunction; group B (n = 13), patients in a minimally conscious state; and group C (n = 17), patients in a vegetative state. rCM patterns on FDG-PET among these groups were evaluated and compared with those of normal control subjects on statistical parametric maps. RESULTS: Hypometabolism was consistently indicated bilaterally in the medial prefrontal regions, the medial frontobasal regions, the cingulate gyrus and the thalamus. Hypometabolism in these regions was the most widespread and prominent in group C, and that in group B was more widespread and prominent than that in group A. CONCLUSIONS: Bilateral hypometabolism in the medial prefrontal regions, the medial frontobasal regions, the cingulate gyrus and the thalamus may reflect the clinical deterioration of TDBI, which is due to functional and structural disconnections of neural networks rather than due to direct cerebral focal contusion.

Adult↗

Cardiovascular responses to V1-vasopressinergic antagonism in conscious versus anesthetized rats.

Experiments were performed to compare the possible effect of endogenous arginine vasopressin on renal hemodynamics between anesthetized, surgically stressed rats and conscious rats. Animals were instrumented with arterial and venous catheters as well as with a pulsed Doppler flow probe on the left renal artery. The rats were studied under the following conditions: (1) conscious and unrestrained; (2) anesthetized only; (3) anesthetized with minor surgical stress; and (4) anesthetized with major surgical stress. Two anesthetic agents were also compared, a mixture of ketamine (110 mg/kg i.m.) and acepromazine (1 mg/kg i.m.), and sodium pentobarbital (50 mg/kg i.p.). Baseline mean arterial blood pressure was significantly higher in pentobarbital-anesthetized rats following surgical stress compared with conscious animals, but blood pressure was not affected by ketamine-acepromazine anesthesia. After baseline measurements of blood pressure, heart rate, and renal blood flow, a specific V1-vasopressinergic antagonist (d(CH2)5Tyr(Me) arginine vasopressin, 10 mg/kg i.v.) was administered to each group. Mean arterial blood pressure, heart rate, and renal blood flow were monitored for an additional 15 min. Mean arterial blood pressure and renal blood flow decreased after V1 antagonism in ketamine-acepromazine-anesthetized rats with major surgical stress, but were not affected in pentobarbital-anesthetized animals. Heart rate and renal vascular resistance were not affected following V1 blockade with either anesthetic agent. These data suggest that arginine vasopressin plays a role in maintaining blood pressure and renal perfusion in ketamine-acepromazine-anesthetized rats following surgical stress, but does not have a significant effect on renal hemodynamics under pentobarbital anesthesia.

Acepromazine↗

Function of vasopressinergic neurons in rats under conscious and anesthetized conditions.

The responses of vasopressinergic neurons to acute salt loading and to graded hemorrhage were studied in rats under conscious and anesthetized conditions. Chronically cannulated rats were used in this study so that pre- and postanesthetic conditions could be studied in the same animals. Anesthesia induced by a combination of ketamine hydrochloride and pentobarbital sodium (Nembutal) did not cause a release of vasopressin-associated neurophysin (VP-RNP). In response to infusion of 18% saline, animals in the anesthetized state had significantly greater increases in plasma osmolality (Posmol) and plasma sodium concentration than animals in the conscious state. However, the rate of increase in plasma VP-RNP concentration ([VP-RNP]) as well as the relationship between [VP-RNP] and Posmol were not significantly different for the two states. Graded hemorrhage caused similar rates of increase in [VP-RNP] for animals under conscious and anesthetized conditions. These data suggest that anesthesia induced by ketamine plus pentobarbital sodium does not change the responsiveness of vasopressinergic neurons to acute salt loading and to graded hemorrhage.

Anesthesia, General↗

Hemodynamic characterization of conscious and ketamine-anesthetized bile duct-ligated rats.

The present study was conducted to characterize the hemodynamic alterations in common bile duct-ligated (CBDL) rats under ketamine anesthesia and in the awake restrained state. Hemodynamic studies using the radioactive microspheres technique were performed 17.6 +/- 0.6 (SE) days after bile duct ligation or sham operation. CBDL rats had lower mean arterial pressure, reduced systemic and renal resistance, and increased renal blood flow compared with sham-operated rats. This was found both in the conscious and anesthetized states. Anesthetized CBDL rats had higher portal pressure (13.2 +/- 0.5 vs. 9.2 +/- 0.4 mmHg; P less than 0.001) and lower splanchnic arteriolar resistance (15.4 +/- 1.3 vs 26.8 +/- 4.6 mmHg.ml-1.min.100 g body wt; P less than 0.05) than sham-operated rats. Portosystemic shunting was 52.3 +/- 11.7% in CBDL and negligible in sham-operated rats. The last three parameters could not be measured in conscious animals. Total peripheral resistance was lower in the conscious than in the anesthetized state, diverting a higher fraction of cardiac output at the expense of splanchnic organs and leading to a significant reduction of portal venous inflow in sham-operated but not in CBDL rats [3.36 +/- 0.47 vs. 5.38 +/- 0.65 (P less than 0.05) and 5.33 +/- 0.58 vs. 6.34 +/- 0.37 ml.min-1.100 g body wt-1 (P = NS), respectively]. These findings indicate that CBDL and normal rats respond differently to anesthesia and restraint. Because the restrained state is stressful and studies in anesthetized animals are technically simpler, provide additional information such as portal pressure and portosystemic shunting, and diminish animal suffering, we suggest that hemodynamic studies in rats, using the microsphere technique, should be preferably performed under ketamine anesthesia.

Anesthesia, General↗

New technique for measurement of left ventricular pressure in conscious mice.

Concern about the effects of anesthesia on physiological measurements led us to develop methodology to assess left ventricular (LV) pressure in conscious mice. Polyethylene-50 tubing filled with heparinized saline was implanted in the LV cavity through its apex via an abdominal approach and exteriorized to the back of the animal. This surgery was done under anesthesia with either an intraperitoneal injection of ketamine (80 mg/kg) and xylazine (5 mg/kg) (K+X) in 11 mice or isoflurane (ISF; 1.5 vol%) by inhalation in 14 mice. Postoperatively, mice were trained daily to lie quietly head first in a plastic cone. LV pressure, the first derivative of LV pressure (dP/dt), and heart rate (HR) in the conscious state were compared between the two groups at 3 days and 1 wk after recovery from surgery using a 1.4-Fr Millar catheter inserted into the LV through the tubing, with the mice lying quietly in the plastic cone. Acutely during anesthesia, K+X decreased HR (from 698 to 298 beats/min), LV systolic pressure (from 107 to 65 mmHg), and maximal dP/dt (dP/dt(max)) (from 15,724 to 4,445 mmHg/s), all P < 0.01. Similar but less marked negative chronotropic and inotropic effects were seen with ISF. HR and dP/dt(max) were decreased significantly in K+X mice 3 days after surgery compared with those anesthetized with ISF (655 vs. 711 beats/min, P < 0.05; 14,448 vs. 18,048 mmHg/s, P < 0.001) but increased to the same level as in ISF mice 1 wk after surgery. In ISF mice, recovery of function occurred rapidly and there were no differences in LV variables between 3 days and 1 wk. LV pressure and dP/dt can be measured in conscious mice with a micromanometer catheter inserted through tubing implanted permanently in the LV apex. Anesthesia with either K+X or, to a lesser extent, ISF, depressed LV function acutely. This depression of function persisted for 3 days after surgery with K+X (but not ISF) and did not recover completely until 1 wk postanesthesia.

Adrenergic alpha-Agonists↗

A self-calibrating telemetry system for measurement of ventricular pressure-volume relations in conscious, freely moving rats.

Using Bluetooth wireless technology, we developed an implantable telemetry system for measurement of the left ventricular pressure-volume relation in conscious, freely moving rats. The telemetry system consisted of a pressure-conductance catheter (1.8-Fr) connected to a small (14-g) fully implantable signal transmitter. To make the system fully telemetric, calibrations such as blood resistivity and parallel conductance were also conducted telemetrically. To estimate blood resistivity, we used four electrodes arranged 0.2 mm apart on the pressure-conductance catheter. To estimate parallel conductance, we used a dual-frequency method. We examined the accuracy of calibrations, stroke volume (SV) measurements, and the reproducibility of the telemetry. The blood resistivity estimated telemetrically agreed with that measured using an ex vivo cuvette method (y=1.09x - 11.9, r2= 0.88, n=10). Parallel conductance estimated by the dual-frequency (2 and 20 kHz) method correlated well with that measured by a conventional saline injection method (y=1.59x - 1.77, r2= 0.87, n=13). The telemetric SV closely correlated with the flowmetric SV during inferior vena cava occlusions (y=0.96x + 7.5, r2=0.96, n=4). In six conscious rats, differences between the repeated telemetries on different days (3 days apart on average) were reasonably small: 13% for end-diastolic volume, 20% for end-systolic volume, 28% for end-diastolic pressure, and 6% for end-systolic pressure. We conclude that the developed telemetry system enables us to estimate the pressure-volume relation with reasonable accuracy and reproducibility in conscious, untethered rats.

Animals↗

Cardioprotection by postconditioning in conscious rats is limited to coronary occlusions <45 min.

OBJECTIVES: Brief episodes of ischemia and reperfusion after a lethal ischemic insult confer cardioprotection, a phenomenon termed "ischemic postconditioning." However, all studies reported to date have been conducted in open-chest animal models. We sought to determine whether postconditioning occurs in conscious animals and whether it protects against severe myocardial injury. METHODS: Chronically instrumented rats were assigned to a 30- (Subset 1), 45- (Subset 2), or 60-min (Subset 3) coronary occlusion followed by 24 h of reperfusion. In each subset, rats received no further intervention (control), were preconditioned with 12 cycles of 2-min occlusion/2-min reperfusion immediately (early preconditioning; EPC) or 24 h (late preconditioning; LPC) before myocardial infarction, or were postconditioned with 20 cycles of 10-s occlusion/10-s reperfusion immediately after myocardial infarction (20-10 PostC). RESULTS: With a 30-min occlusion, infarct size (54.4 +/- 2.3% of risk region in control-30) was significantly reduced in EPC-30, LPC-30, and 20-10 PostC-30 groups (by 72, 70, and 47%, respectively; all P < 0.05 vs. control-30). With a 45-min occlusion, infarct size (62.2 +/- 2.4% in control-45) was reduced in EPC-45 and LPC-45 groups (by 47 and 41%, respectively; all P < 0.05 vs. control-45) but not in the 20-10 PostC-45 group [55.4 +/- 2.3%, P = not significant (NS) vs. control-45]. With a 60-min occlusion, infarct size (72.7 +/- 2.2% in control-60) was reduced in the EPC-60 (by 20%, P < 0.05) but not in the LPC-60 (63.6 +/- 2.5%, P = NS) or in the 20-20 PostC group (71.5 +/- 3.4%, P = NS). CONCLUSIONS: Both early and late ischemic preconditioning as well as ischemic postconditioning confer protection in conscious rats; however, unlike early preconditioning, postconditioning protects only against coronary occlusions <45 min. In the conscious rat, the cardioprotection afforded by postconditioning is limited to mild to moderate myocardial injury.

Animals↗

Left ventricular pressure-volume relationship in conscious mice.

With the availability of transgenic models, the mouse has become an increasingly important subject for genetic-hemodynamic studies. Recently, we developed a technique to measure left ventricular (LV) pressure in conscious mice with an implanted LV polyethylene tube. We extended our new method by evaluating the LV pressure-volume relationship and examined the feasibility of this method in this study. We studied 17 male mice (age, 11-20 wk) with a conductance catheter inserted into the LV through the polyethylene tube. Load-independent parameters of contractility derived from pressure-volume relationship [slope of the end-systolic pressure-volume relationship (E(es)), slope of the maximum first derivative of LV pressure (dP/dt(max))-end-diastolic volume (EDV) relation, and preload-recruitable stroke work (PRSW)] were evaluated by inferior vena caval occlusion with an implanted snare. LV function assessed by this technique on two different days showed that the parameters were very similar, indicating reproducibility. Both linear and nonlinear regression analyses were performed for E(es). Contractility was enhanced by isoproterenol (E(es), 13.1 +/- 6.6 to 20.8 +/- 8.7 mmHg/microl; dP/dt(max)-EDV, 496 +/- 139 to 825 +/- 178 mmHg.s(-1).microl(-1); and PRSW, 110 +/- 23 to 127 +/- 21 mmHg), depressed by atenolol (E(es), 14.5 +/- 6.1 to 4.6 +/- 2.0 mmHg/microl; dP/dt(max)-EDV, 543 +/- 188 to 185 +/- 94 mmHg.s(-1).microl(-1); and PRSW, 117 +/- 20 to 70 +/- 15 mmHg) and isoflurane (E(es), 12.3 +/- 6.0 to 5.7 +/- 2.1 mmHg/microl; dP/dt(max)-EDV, 528 +/- 172 to 164 +/- 68 mmHg/s.microl; and PRSW, 124 +/- 19 to 48 +/- 10 mmHg), significantly. In conclusion, this is the first description of the LV pressure-volume relationship in conscious mice. These findings suggest that this method is feasible to detect changes of contractility in the conscious state, allowing serial assessment of pressure-volume-derived cardiac function indexes over time without anesthesia or repeated surgery.

Animals↗

Sex differences in the development of angiotensin II-induced hypertension in conscious mice.

Sex has an important influence on blood pressure (BP) regulation. There is increasing evidence that sex hormones interfere with the renin-angiotensin system. Thus the purpose of this study was to determine whether there are sex differences in the development of ANG II-induced hypertension in conscious male and female mice. We used telemetry implants to measure aortic BP and heart rate (HR) in conscious, freely moving animals. ANG II (800 ng.kg(-1).min(-1)) was delivered via an osmotic pump implanted subcutaneously. Our results showed baseline BP in male and female mice to be similar. Chronic systemic infusion of ANG II induced a greater increase in BP in male (35.1 +/- 5.7 mmHg) than in female mice (7.2 +/- 2.0 mmHg). Gonadectomy attenuated ANG II-induced hypertension in male mice (15.2 +/- 2.4 mmHg) and augmented it in female mice (23.1 +/- 1.0 mmHg). Baseline HR was significantly higher in females relative to males (630.1 +/- 7.9 vs. 544.8 +/- 16.2 beats/min). In females, ANG II infusion significantly decreased HR. However, the increase in BP with ANG II did not result in the expected decrease in HR in either intact male or gonadectomized mice. Moreover, the slope of the baroreflex bradycardia to phenylephrine was blunted in males (-5.6 +/- 0.3 to -2.9 +/- 0.5) but not in females (-6.5 +/- 0.5 to -5.6 +/- 0.3) during infusion of ANG II, suggesting that, in male mice, infusion of ANG II results in a resetting of the baroreflex control of HR. Ganglionic blockade resulted in greater reduction in BP on day 7 after ANG II infusion in males compared with females (-61.0 +/- 8.9 vs. -36.6 +/- 6.6 mmHg), suggesting an increased contribution of sympathetic nerve activity in arterial BP maintenance in male mice. Together, these data indicate that there are sex differences in the development of chronic ANG II-induced hypertension in conscious mice and that females may be protected from the increases in BP induced by ANG II.

Angiotensin II↗

Stimulation and blockade of GABA(A) receptors in the raphe pallidus: effects on body temperature, heart rate, and blood pressure in conscious rats.

Studies in anesthetized rats have implicated GABAA receptors in the region of the medullary raphe pallidus (RP) at the level of the facial nucleus in sympathetic nervous regulation of both heart rate and thermoregulatory mechanisms. Therefore, we examined the effect of microinjection of muscimol, a GABAA receptor agonist, and of bicuculline methiodide (BMI), a GABAA receptor antagonist, into the same region of the RP on heart rate, blood pressure, and core body temperature in conscious rats. Microinjection of BMI (40 pmol) into the RP evoked tachycardia that appeared within 1 min and was maximal within 10 min but had little or no effect on blood pressure or body temperature. Microinjection of muscimol (10-80 pmol) at the same sites in the RP evoked marked dose-related decreases in body temperature that developed more slowly (i.e., maximum decreases appearing at 60-75 min after 80 pmol) but had no effect on heart rate or blood pressure. Injection of either agent at sites outside the region had lesser or no effect on the measured parameters. These findings suggest that activity of neurons in the region of the RP plays an important role in the maintenance of body temperature but not heart rate under baseline conditions in conscious rats. Specifically, thermoregulatory neurons in this region appear to be tonically active and contribute to maintenance of body temperature under baseline conditions, while cardiac sympathetic premotor neurons in the RP are not active under these circumstances and thus do not support basal heart rate in conscious rats.

Animals↗

Renin, ACTH, and aldosterone during acute hypercapnia and hypoxia in conscious rats.

The control of aldosterone secretion may be altered during acute changes in arterial blood gases. We studied the blood gas, plasma electrolyte, renin (PRA), adrenocorticotropic hormone (ACTH), and aldosterone (ALDO) responses to acute hypercapnia (4 and 8% CO2), acute hypocapnic hypoxia (10% O2), acute severe normocapnic hypoxia (7% O2-4% CO2), and acute hypercapnic hypoxia (7% O2-8% CO2) in conscious, cannulated Long-Evans rats. Normoxia resulted in normal levels of PRA (6.9 +/- 2.0 ng.ml-1.h-1), ACTH (96 +/- 32 pg/ml), and ALDO (10 +/- 3 ng/dl). Hypercapnia had no effect on PRA but did lead to an increase in ACTH (to 298 +/- 69 pg/ml) and ALDO (to 33 +/- 7 ng/dl) during 8% CO2 exposure. Normocapnic hypoxia resulted in a significant increase in ACTH (to 196 +/- 14 pg/ml) and ALDO (to 30 +/- 3 ng/dl). Hypercapnic hypoxia resulted in the greatest increases in PRA (to 30 +/- 2 ng.ml-1.h-1), ACTH (to 397 +/- 114 pg/ml), and ALDO (to 41 +/- 5 ng/dl). We conclude that in conscious rats 1) hypercapnia (less than 80 Torr) had no significant effect on PRA, 2) isocapnic, severe hypoxia (Po2 approximately 34 Torr) increased ACTH, and 3) the combination of hypercapnia and hypoxia was a very potent stimulus to PRA, ACTH, and ALDO. The ALDO responses to increases in endogenous ACTH and angiotensin II appear to be normal in conscious rats during acute hypoxia and/or hypercapnia.

Acute Disease↗