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 1,657 records · Page 92Linked to original sources
PubMed2000

Carotid and cardiopulmonary chemoreceptor activity increases hippocampal theta rhythm in conscious rabbits.

We have examined whether activation of carotid artery chemoreceptors causes alerting in conscious rabbits. Injection of phenylbiguanide (a 5-hydroxytryptamine(3)-receptor agonist) into the common carotid artery of conscious rabbits increased the proportion of theta rhythm in the hippocampal EEG, commencing in the first 5-s epoch after the injection. Intravenous injection of phenylbiguanide also increased the proportion of theta rhythm in the hippocampal electroencephalogram (EEG), but the onset of the change was not until the second 5-s epoch following injection. Injection of Ringer solution, either into the common carotid artery or into the marginal ear vein, did not affect the hippocampal EEG. Results suggest that phenylbiguanide-mediated activation of carotid and cardiopulmonary chemoreceptor afferents alerts the animal, as assessed by induction of theta rhythm in the hippocampal EEG. This alerting response presumably reflects the action of neural inputs that enter the brain with the carotid sinus nerve at the level of the medulla oblongata.

Anesthesia↗
PubMed2001

ANP, BNP, and CNP enhance bradycardic responses to cardiopulmonary chemoreceptor activation in conscious sheep.

We demonstrated previously that atrial natriuretic peptide (ANP) enhances reflex bradycardia to intravenous serotonin [5-hydroxytryptamine (5-HT)] (von Bezold-Jarisch reflex) in rats. To determine whether 1) ANP affects this cardiopulmonary vagal reflex in another species and 2) B-type (BNP) and C-type (CNP) natriuretic peptides share with ANP the ability to modulate this reflex, we used intravenous phenylbiguanide (PBG), a 5-HT(3) agonist, as the stimulus to evoke a von Bezold-Jarisch reflex (dose-related, reproducible bradycardia) in conscious adult sheep (n = 5). Three doses of PBG (13 +/- 3, 20 +/- 3, and 31 +/- 4 microg/kg) injected into the jugular vein caused reflex cardiac slowing of -7 +/- 1, -15 +/- 2, and -36 +/- 3 beats/min, respectively, under control conditions. These doses of PBG were repeated during infusions of ANP, BNP, or CNP (10 pmol. kg(-1). min(-1) iv), or vehicle (normal saline). Each of the natriuretic peptides significantly (P < 0.05) enhanced the sensitivity of bradycardic responses to PBG by 94 +/- 8% (ANP), 142 +/- 55% (BNP), and 61 +/- 16% (CNP). Thus not only did ANP sensitize cardiopulmonary chemoreceptor activation in a species with resting heart rate close to that in humans, but BNP and CNP also enhanced von Bezold-Jarisch reflex activity in conscious sheep.

Animals↗
PubMed2003

Serial determination of glomerular filtration rate in conscious mice using FITC-inulin clearance.

Two nonradioactive methods for determining glomerular filtration rate (GFR) in conscious mice using FITC-labeled inulin (FITC-inulin) were evaluated. The first method measured GFR using clearance kinetics of plasma FITC-inulin after a single bolus injection. Based on a two-compartment model, estimated GFR was 236.69 +/- 16.55 and 140.20 +/- 22.27 microl/min in male and female C57BL/6J mice, respectively. Total or (5/6) nephrectomy reduced inulin clearance to 0 or 32.80 +/- 9.32 microl/min, respectively. Conversely, diabetes mellitus induced by streptozotocin was associated with increased GFR. The other approach measured urinary inulin clearance using intraperitoneal microosmotic pumps to deliver FITC-inulin and metabolic cages to collect timed urine samples. This approach yielded similar GFR values of 211.11 +/- 26.56 and 157.36 +/- 20.02 microl/min in male and female mice, respectively. These studies demonstrate the feasibility of repeated nonisotopic measurement of inulin clearance in conscious mice.

Animals↗
PubMed2002

Spontaneous renal blood flow autoregulation curves in conscious sinoaortic baroreceptor-denervated rats.

These experiments examined whether the conscious sinoaortic baroreceptor-denervated (SAD) rat, owing to its high spontaneous arterial pressure (AP) variability, might represent a model for renal blood flow (RBF) autoregulation studies. In eight SAD and six baroreceptor-intact rats, AP and RBF were recorded (1-h periods) before and after furosemide (10 mg/kg followed by 10 mg. kg(-1). h(-1) iv) administration. In control conditions, AP variability was markedly enhanced in SAD rats (coefficient of variation: 16.0 +/- 1.2 vs. 5.4 +/- 0.5% in intact rats), whereas RBF variability was only slightly increased (8.7 +/- 0.6 vs. 6.1 +/- 0.5% in intact rats), suggesting buffering by autoregulatory mechanisms. In SAD rats, but not in intact rats, the AP-RBF relationships could be modeled with a four-parameter sigmoid Weibull equation (r(2) = 0.24 +/- 0.07, 3,600 data pairs/rat), allowing for estimation of an autoregulatory plateau (10.1 +/- 0.7 ml/min) and a lower limit of RBF autoregulation (P(LL) = 93 +/- 6 mmHg, defined as AP at RBF 5% below the plateau). After furosemide treatment, autoregulation curves (r(2) = 0.49 +/- 0.07) in SAD rats were shifted downward (plateau = 8.6 +/- 0.8 ml/min) and rightward (P(LL) = 102 +/- 5 mmHg). In five of six intact rats, P(LL) became measurable (104 +/- 1 mmHg), albeit with limited accuracy (r(2) = 0.09 +/- 0.03). In conclusion, the conscious SAD rat offers the possibility of describing RBF autoregulation curves under dynamic, unforced conditions. The tubuloglomerular feedback and myogenic mechanisms cooperate in setting P(LL) and thus in stabilizing RBF during spontaneous depressor episodes.

Animals↗
PubMed1981

Adrenergically induced renin release in conscious indomethacin-treated dogs and rats.

To investigate the role of endogenous prostaglandins in renin release stimulated via adrenergic pathways, isoproterenol, norepinephrine (NE) and NE in the presence of phentolamine (PTA) were infused into conscious sodium-replete rats and dogs. Isoproterenol (1 microgram.kg-1.min-1) infusion into intact rats increased plasma renin activity (PRA) eightfold. AFter pretreatment with the prostaglandin (PG) cyclooxygenase inhibitor indomethacin (5 mg/kg), isoproterenol increased PRA 16-fold. In dogs, isoproterenol (0.4 microgram.kg-1.min-1) increased PRA six-fold before indomethacin and 11-fold during PG inhibition. Infusion of NE into both rats (250 ng.kg-1.min-1) and dogs (1 microgram.kg-1.min-1) failed to increase PRA before indomethacin, but during inhibition of PG synthesis NE increased PRA in both species. During partial alpha-adrenergic blockade with PTA in dogs, PTA alone increased PRA by 38% and NE given during PTA infusion increased PRA further both before indomethacin by twofold and during PG inhibition by fivefold. In rats given NE during PTA infusion, PRA increased only after indomethacin injection. Additionally, in dogs the renin responses to these adrenergic agents were even greater after indomethacin administration than before the drug. These results in both conscious rats and dogs give no indication that renal prostaglandins mediate the renin response to adrenergic stimulation.

Animals↗
PubMed1983

Hemodynamic mechanisms in CNS-induced natriuresis in the conscious rat.

These experiments were designed to determine 1) the effects of increased CSF sodium concentration on renal hemodynamics in the conscious rat, and 2) the role of the periventricular tissue surrounding the anteroventral third ventricle (AV3V) in the natriuretic and hemodynamic responses during this treatment. After electrolytic lesions of AV3V periventricular tissue or control surgery, blood pressure, glomerular filtration rate, effective renal blood flow, urine volume, and sodium and potassium excretion were measured before and during intraventricular (IVT) infusion of either isotonic or hypertonic saline solutions in conscious hydrated rats. Blood pressure, glomerular filtration rate, and sodium and potassium excretion increased during IVT infusion of concentrated sodium solutions in control rats but not in animals with lesions in the AV3V region. These data support the hypothesis that the natriuretic response to increased CSF sodium concentration in the rat is due to a pressor response and/or increased glomerular filtration rate and demonstrate that ablation of AV3V periventricular tissue blunts the natriuretic response, possibly through diminished central pressor mechanisms and/or decreased central control of glomerular filtration rate.

Animals↗
PubMed1984

Effect of renal denervation on the suppression of renin secretion by vasopressin in conscious dogs.

Previous studies have shown that the inhibition of renin secretion by vasopressin (AVP) in conscious dogs is related to vasoconstrictor activity and may be a reflex response mediated by the renal nerves. The aim of the present experiments was to determine whether the suppression of plasma renin activity (PRA) by AVP is blocked by renal denervation. AVP and, for comparison, angiotensin II (ANG II) were infused intravenously for 45 min in seven conscious dogs before and after bilateral renal denervation. Before denervation, AVP infusion at 0.2 and 1.0 ng X kg-1 X min-1 suppressed PRA from 7.4 +/- 1.1 to 4.7 +/- 1.0 (P less than 0.01) and from 7.9 +/- 1.8 to 3.8 +/- 0.8 ng X ml-1 X 3 h-1 (P less than 0.01), respectively. ANG II infusion at 5.0 and 10.0 ng X kg-1 X min-1 decreased PRA from 7.5 +/- 2.3 to 2.5 +/- 0.7 (P less than 0.01) and from 6.0 +/- 1.1 to 1.8 +/- 0.4 ng X ml-1 X 3 h-1 (P less than 0.01), respectively. One to three weeks following renal denervation, PRA had decreased from 6.7 +/- 1.3 to 2.9 +/- 0.5 ng X ml-1 X 3 h-1 (P less than 0.01), and renal norepinephrine was undetectable. After denervation, neither AVP infusion at 0.2 (3.0 +/- 0.5 to 2.4 +/- 0.4 ng X ml-1 X 3 h-1) nor 1.0 ng X kg-1 X min-1 (3.1 +/- 0.8 to 2.8 +/- 1.0 ng X ml-1 X 3 h-1) suppressed PRA.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1986

Renal hemodynamics and arterial pressure during chronic intrarenal adenosine infusion in conscious dogs.

The major aim of this study was to examine the chronic effects of increased intrarenal adenosine (ADO) levels on control of renal hemodynamics and mean arterial pressure (MAP). In six uninephrectomized conscious dogs, intrarenal ADO infusion (2 micrograms . kg-1 . min-1) for 6 days caused no significant changes in MAP, which averaged 94 +/- 3 mmHg during the control period and 91 +/- 2 mmHg during ADO infusion. ADO infusion for 6 days decreased glomerular filtration rate (GFR) and filtration fraction while causing no significant changes in effective renal plasma flow (ERPF) or sodium and water balance. To examine the role of angiotensin II (ANG II) in altering the blood pressure and renal effects of ADO, we also studied the effects of intrarenal ADO infusion in five uninephrectomized conscious dogs during continuous intrarenal infusion of ANG II (1 ng . kg-1 . min-1) to prevent renal levels of ANG II from decreasing. However, even when renal ANG II levels were maintained constant, ADO infusion at 2 micrograms . kg-1 . min-1 for 4 days and 10 micrograms . kg-1 . min-1 for 5 days failed to alter MAP, which averaged 104 +/- 6 mmHg during the control period, 106 +/- 5 mmHg during infusion of 2 micrograms . kg-1 . min-1, and 105 +/- 5 mmHg during infusion of 10 micrograms. . kg-1 . min-1 ADO. Intrarenal ANG II infusion did not prevent decreases in GFR and filtration fraction during ADO infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1986

Role of the vasoconstrictor and antidiuretic activities of vasopressin in inhibition of renin secretion in conscious dogs.

The nature of the activity of vasopressin that is responsible for the inhibition of renin secretion was studied in normally hydrated conscious dogs using intravenous infusions of vasopressin and analogues of vasopressin with selective antidiuretic and vasoconstrictor activity. Vasopressin (1.0 ng . kg-1 . min-1) increased mean arterial pressure (MAP) from 106 +/- 2 to 115 +/- 3 mmHg (P less than 0.05) and decreased heart rate (HR) from 81 +/- 6 to 56 +/- 5 beats/min (P less than 0.001). Plasma renin activity (PRA) decreased from 4.4 +/- 1.1 to 2.4 +/- 0.8 ng . ml-1 . 3 h-1 (P less than 0.05). A specific antagonist of the vasoconstrictor activity of vasopressin, d(CH2)5MeTyrAVP (10 micrograms/kg), completely blocked the cardiovascular and renin responses to vasopressin. A selective vasoconstrictor agonist, 2-phenylalanine-8-ornithine oxytocin (1.0 ng . kg-1 . min-1), increased MAP from 112 +/- 4 to 128 +/- 6 mmHg (P less than 0.001) and decreased HR from 69 +/- 3 to 47 +/- 4 beats/min (P less than 0.001). PRA decreased from 5.5 +/- 1.1 to 2.7 +/- 0.2 ng . ml-1 X 3 h-1 (P less than 0.001). In contrast, a selective antidiuretic agonist, 1-deamino-8-D-arginine vasopressin (1.0 ng . kg-1 . min-1) did not alter PRA, MAP, or HR. These results demonstrate that the acute inhibition of renin secretion by vasopressin in normally hydrated conscious dogs is due to vasoconstrictor rather than antidiuretic activity.

Animals↗
PubMed1990

Intracoronary veratrine and acute aortic stenosis modify renal responses to hypotension in conscious dogs.

The present study was undertaken to determine whether intracoronary (left circumflex) veratrine (ICV) infusions and increases in left ventricular (LV) systolic pressure influence renal circulatory and excretory function in chronically instrumented conscious dogs (n = 19). Thirty minutes of ICV infusions decreased arterial pressure by 15-20 mmHg, but heart rate, urine flow, sodium excretion, and free water clearance did not change. Intravenous nitroprusside infusions, which also lowered arterial pressure by 15-20 mmHg, increased heart rate while urine flow, sodium excretion, and free water clearance were significantly decreased. Heart rate and renal excretory function also did not change during a 15- to 20-mmHg decrease in arterial pressure when LV systolic pressure was simultaneously raised to approximately 170 mmHg by ascending aortic occlusion. The topical application of a local anesthetic in the region of the left main coronary artery abolished the Bezold-Jarisch reflex and the attenuation of hypotension-induced salt and water retention and tachycardia by ICV. Renal plasma flow and glomerular filtration rate were not altered during any of the above experimental treatments. These results suggest that in the conscious dog chemical and mechanical stimulation of LV sensory receptors with afferents in the pericoronary region can modulate the neurohumoral reflex control of renal excretory function independent of local filtration effects.

Animals↗
PubMed1983

Control of respiratory pattern in conscious dog: effects of heat and CO2.

We measured tidal volume (VT) and inspiratory (TI) and expiratory (TE) durations in five conscious tracheostomized dogs breathing air or 5% CO2 in air either at normal (20 degrees C) or elevated (30 degrees C) ambient temperatures. Respiratory frequency ranged between 16 and 333/min due to changes in both TI and TE. During panting TI exceeded TE. During air inhalation instantaneous ventilation (V) spontaneously ranged from 100 to 1,600 ml . kg-1 . min-1. Hypercapnia, heat stress, or both, increased this range of V by increasing maximum V, primarily due to increases in mean inspiratory flow. Under these conditions, changes in TI accounted for more of the spontaneous changes in breath duration. During inhalation of air and 5% CO2, a positive correlation between VT and TI was obtained for TI between 0.13 and 1.05 s; above 1.05 s VT decreased. Heat stress increased VT at a given TI. We suggest that either the decay rate or position of the inspiratory off-switch threshold curve (Clark and von Euler, J. Physiol. London 222: 267, 1972) varies in conscious dogs. Shifts in either the reset (onset) value or decay rate of the curve yield a positive correlation between VT and TI. This modification to the Clark-von Euler model implies that the primary effect of anesthesia on respiratory control is fixation of the inspiratory off-switch threshold curve.

Animals↗
PubMed1986

Neural antagonists modulate pulmonary vascular pressure-flow plots in conscious dogs.

Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed in conscious dogs during normoxia by graded constriction of the thoracic inferior vena cava to reduce Q. P/Q plots were generated with the autonomic nervous system (ANS) intact and following total autonomic ganglionic block, cholinergic block, and sympathetic alpha- and beta-adrenergic block alone and in combination. With the ANS intact, the relationship between the pulmonary vascular pressure gradient [pulmonary arterial pressure (PAP)--pulmonary capillary wedge pressure (PCWP)] and Q was linear with an extrapolated pressure intercept of 0 mmHg. Total autonomic ganglionic block increased PAP-PCWP over the entire range of Q studied (60-140 ml . min-1 . kg-1). Cholinergic block resulted in a small increase in PAP-PCWP at a Q of 60 ml . min-1 . kg-1, a small decrease in PAP-PCWP at a Q of 140 ml . min-1 . kg-1, but no change in PAP-PCWP over the midrange of Q. Sympathetic beta-adrenergic block increased, and sympathetic alpha-adrenergic block decreased PAP-PCWP over the entire range of Q studied. Combined sympathetic alpha- and beta-adrenergic block also increased PAP-PCWP at each level of Q. Thus the ANS, either directly or via circulating catecholamines, exerts an active regulatory influence on the pulmonary vascular P/Q relationship of intact conscious dogs during normoxia over a wide range of Q. Activation of sympathetic beta-adrenergic receptors results in pulmonary vasodilatation, whereas, alpha-receptor activation results in vasoconstriction. Surprisingly, based on the effects of total autonomic ganglionic block and combined sympathetic alpha- and beta-adrenergic block, the net effect of the ANS on PAP-PCWP/Q during normoxia appears to be pulmonary vasodilatation.

Adrenergic alpha-Antagonists↗
PubMed1986

Atropine: no effect on exercise muscle hyperemia in conscious rats.

The purpose of this study was to test the hypothesis that muscarinic cholinergic receptors are involved in the initial vasodilation in red muscle vascular beds of conscious rats performing slow locomotory exercise. Atropine sulfate (1 mg/kg, ia) was administered to one group of rats in which distribution of cardiac output was estimated with radiolabeled microspheres immediately before exercise while the animals were standing on the treadmill and at 30 s and 5 min of treadmill walking at 15 m/min. Blood flows within and among muscles in the atropine-treated animals were compared with flows in control rats that were given a sham injection of an equal volume of physiological saline. Heart rates were elevated above those of control animals in the atropinized rats during preexercise (+17%) and at 30 s of exercise (+15%). However, distributions and magnitudes of blood flows in nonmuscular tissues and within and among skeletal muscles were the same (P greater than 0.05) in atropinized and control rats during preexercise and at both exercise times, indicating that atropine had no effect on the distribution of cardiac output in the rats. It is concluded that muscarinic cholinergic receptors do not play a significant role in elevating muscle blood flow in conscious rats, either during the preexercise anticipatory phase or during slow locomotory exercise.

Animals↗
PubMed1987

Constant-flow perfusion of the hindlimb vascular bed in conscious dogs.

Hindlimb vascular bed pressure-flow relationships were evaluated in seven conscious dogs using a newly developed controlled-flow perfusion technique. For controlled-flow perfusion, blood was diverted from a common carotid artery to a roller pump for perfusion of the left hindlimb vascular bed via an artificial vascular graft anastomosed to the left external iliac artery. An occlusion cuff positioned around the external iliac artery proximal to the graft arrested normal hindlimb blood flow during perfusion. Collateral flow was minimized by ligating all other major arteries supplying the left hindlimb. Hindlimb perfusion pressure, measured via the left deep femoral artery, decreased to a plateau value of 19.7 +/- 3.4 mmHg when pump flow was zero. Pressure-flow relationships were evaluated while the dogs were at rest by changing flow in small "square-wave" steps for 3 min each and measuring the steady-state perfusion pressure at each step. The hindlimb was perfused over a wide range of flows (25-450 ml/min) that resulted in perfusion pressures ranging from 40 to 175 mmHg. The hindlimb pressure-flow relationship obtained was indicative of net passive vascular behavior. That is, resistance to flow decreased with increases in flow, such that a curvilinear pressure-flow relationship occurred that was convex to the pressure axis. We conclude that the hindlimb circulation of resting conscious dogs can be perfused using controlled-flow perfusion techniques. These techniques can also be applied to other vascular beds and should be useful for evaluating peripheral vascular responses to drugs and reflexogenic alterations.

Animals↗
PubMed2000

Pulmonary vasoregulation by endothelin in conscious dogs after left lung transplantation.

We tested the hypothesis that regulation of the pulmonary circulation by endogenous endothelin (ET) during normoxia and hypoxia was altered in conscious dogs 1 mo after left lung autotransplantation (LLA). Sham-operated control and post-LLA dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LP-Q) relationship. LP-Q plots were generated on separate days during normoxia and hypoxia (arterial PO(2) approximately 50 Torr) in the intact condition, after selective ET(A)-receptor inhibition (BQ-485), and after combined ET(A+B)-receptor inhibition (bosentan). Although LLA resulted in a chronic increase in pulmonary vascular resistance, the ET-receptor antagonists had no effect on the LP-Q relationship during normoxia in either group. The magnitude of hypoxic pulmonary vasoconstriction (HPV) was flow dependent in both groups, and the HPV response was potentiated post-LLA compared with control. ET(A)-receptor inhibition attenuated the HPV response to the same extent in both groups. ET(A+B)-receptor inhibition attenuated the HPV response to a greater extent than did ET(A)-receptor inhibition alone, and this effect was greater post-LLA compared with control. Plasma ET-1 concentration only increased during hypoxia in the LLA group. These results indicate that ET does not regulate the baseline LP-Q relationship in either group. Both ET(A)- and ET(B)-receptor activation mediate a component of HPV in conscious dogs, and the vasoconstrictor influence of ET(B)-receptor activation is enhanced post-LLA.

Animals↗
PubMed2001

Evidence that the renin decrease during hypoxia is adenosine mediated in conscious dogs.

This study investigated whether adenosine mediates the decrease in plasma renin activity (PRA) during acute hypoxia. Eight chronically tracheotomized, conscious beagle dogs were kept under standardized environmental conditions and received a low-sodium diet (0.5 mmol.kg body wt(-1).day(-1)). During the experiments, the dogs were breathing spontaneously via a ventilator circuit: first hour, normoxia (21% inspiratory concentration of O(2)); second and third hours, hypoxia (10% inspiratory concentration of O(2)). Each of the eight dogs was studied twice in randomized order in control and theophylline experiments. In theophylline experiments, theophylline, an A(1)-receptor antagonist, was infused intravenously during hypoxia (loading dose: 3 mg/kg within 30 min, maintenance: 0.5 mg. kg(-1). h(-1)). In theophylline experiments, PRA (5.9 +/- 0.8 ng ANG I. ml(-1). h(-1)) and ANG II plasma concentration (15.9 +/- 2.3 pg/ml) did not decrease during hypoxia, whereas plasma aldosterone concentration decreased from 277 +/- 63 to 132 +/- 23 pg/ml (P < 0.05). In control experiments, PRA decreased from 6.8 +/- 0.8 during normoxia to 3.0 +/- 0.5 ng ANG I. ml(-1). h(-1) during hypoxia, ANG II decreased from 13.3 +/- 1.9 to 7.3 +/- 1.9 pg/ml, and plasma aldosterone concentration decreased from 316 +/- 50 to 70 +/- 13 pg/ml (P < 0.05). Thus infusion of the adenosine receptor antagonist theophylline inhibited the suppression of the renin-angiotensin system during acute hypoxia. The decrease in aldosterone occurred independently and is apparently directly related to hypoxia. In conclusion, it is likely that adenosine mediates the decrease in PRA during acute hypoxia in conscious dogs.

Acute Disease↗
PubMed2006

Restrained whole body plethysmography for measure of strain-specific and allergen-induced airway responsiveness in conscious mice.

The mouse is the most extensively studied animal species in respiratory research, yet the technologies available to assess airway function in conscious mice are not universally accepted. We hypothesized that whole body plethysmography employing noninvasive restraint (RWBP) could be used to quantify specific airway resistance (sRaw-RWBP) and airway responsiveness in conscious mice. Methacholine responses were compared using sRaw-RWBP vs. airway resistance by the forced oscillation technique (Raw-FOT) in groups of C57, A/J, and BALB/c mice. sRaw-RWBP was also compared with sRaw derived from double chamber plethysmography (sRaw-DCP) in BALB/c. Finally, airway responsiveness following allergen challenge in BALB/c was measured using RWBP. sRaw-RWBP in C57, A/J, and BALB/c mice was 0.51 +/- 0.03, 0.68 +/- 0.03, and 0.63 +/- 0.05 cm/s, respectively. sRaw derived from Raw-FOT and functional residual capacity (Raw*functional residual capacity) was 0.095 cm/s, approximately one-fifth of sRaw-RWBP in C57 mice. The intra- and interanimal coefficients of variations were similar between sRaw-RWBP (6.8 and 20.1%) and Raw-FOT (3.4 and 20.1%, respectively). The order of airway responsiveness employing sRaw-RWBP was AJ > BALBc > C57 and for Raw-FOT was AJ > BALB/c = C57. There was no difference between the airway responsiveness assessed by RWBP vs. DCP; however, baseline sRaw-RWBP was significantly lower than sRaw-DCP. Allergen challenge caused a progressive decrease in the provocative concentration of methacholine that increased sRaw to 175% postsaline values based on sRaw-RWBP. In conclusion, the technique of RWBP was rapid, reproducible, and easy to perform. Airway responsiveness measured using RWBP, DCP, and FOT was equivalent. Allergen responses could be followed longitudinally, which may provide greater insight into the pathogenesis of chronic airway disease.

Administration, Inhalation↗
PubMed2004

Acetazolamide prevents hypoxic pulmonary vasoconstriction in conscious dogs.

Acute hypoxia increases pulmonary arterial pressure and vascular resistance. Previous studies in isolated smooth muscle and perfused lungs have shown that carbonic anhydrase (CA) inhibition reduces the speed and magnitude of hypoxic pulmonary vasoconstriction (HPV). We studied whether CA inhibition by acetazolamide (Acz) is able to prevent HPV in the unanesthetized animal. Ten chronically tracheotomized, conscious dogs were investigated in three protocols. In all protocols, the dogs breathed 21% O(2) for the first hour and then 8 or 10% O(2) for the next 4 h spontaneously via a ventilator circuit. The protocols were as follows: protocol 1: controls given no Acz, inspired O(2) fraction (Fi(O(2))) = 0.10; protocol 2: Acz infused intravenously (250-mg bolus, followed by 167 microg.kg(-1).min(-1) continuously), Fi(O(2)) = 0.10; protocol 3: Acz given as above, but with Fi(O(2)) reduced to 0.08 to match the arterial Po(2) (Pa(O(2))) observed during hypoxia in controls. Pa(O(2)) was 37 Torr during hypoxia in controls, mean pulmonary arterial pressure increased from 17 +/- 1 to 23 +/- 1 mmHg, and pulmonary vascular resistance increased from 464 +/- 26 to 679 +/- 40 dyn.s(-1).cm(-5) (P < 0.05). In both Acz groups, mean pulmonary arterial pressure was 15 +/- 1 mmHg, and pulmonary vascular resistance ranged between 420 and 440 dyn.s(-1).cm(-5). These values did not change during hypoxia. In dogs given Acz at 10% O(2), the arterial Pa(O(2)) was 50 Torr owing to hyperventilation, whereas in those breathing 8% O(2) the Pa(O(2)) was 37 Torr, equivalent to controls. In conclusion, Acz prevents HPV in conscious spontaneously breathing dogs. The effect is not due to Acz-induced hyperventilation and higher alveolar Po(2), nor to changes in plasma endothelin-1, angiotensin-II, or potassium, and HPV suppression occurs despite the systemic acidosis with CA inhibition.

Acetazolamide↗