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At least 775 records · Page 43Linked to original sources
PubMed1993

Prostanoids promote pial arteriolar dilation and mask constriction to oxytocin in piglets.

We determined effects of oxytocin on piglet pial arterioles and the role of prostanoids in mediating arteriolar responses. Anesthetized piglets were equipped with closed cranial windows, and arteriolar diameter was measured using intravital microscopy. Pial arterioles were exposed to 10(-10) to 10(-4) M oxytocin. Cerebrospinal fluid (CSF) levels of prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) were determined using radioimmunoassay. Baseline diameter was 110 +/- 4 microns and increased to 120 +/- 6 microns at 10(-8) M (9 +/- 3%, n = 20). CSF levels of PGE2 were 697 pg/ml during baseline and increased to 1,685 +/- 316 pg/ml during 10(-6) M, 2,243 +/- 327 pg/ml during 10(-5) M, and 2,941 +/- 500 pg/ml during 10(-4) (n = 6). CSF levels of 6-keto-PGF1 alpha were 354 +/- 73 pg/ml during baseline and increased to 734 +/- 168 pg/ml at 10(-5) M and to 836 +/- 167 pg/ml at 10(-4) M (n = 5). After inhibition of prostaglandin synthesis by indomethacin (5 mg/kg i.v.), oxytocin constricted at all doses, starting at 10(-10) M (5 +/- 2%) and continuing to constrict at 10(-4) M (24 +/- 2%, n = 14). We conclude that: 1) piglet pial arterioles respond to relatively low levels of oxytocin, 2) local presence and/or production of prostanoids promotes dilation, and 3) endogenous prostanoids prevent constriction of pial arterioles to oxytocin. Our results suggest that oxytocin could play a role in the regulation of cerebral hemodynamics.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

A novel model of conduit coronary constriction reveals local actions of endothelin-1 and prostaglandin F2alpha.

We evaluated the effects of endothelin-1 (ET-1) and prostaglandin F2alpha (PGF2alpha) selectively on conduit coronary artery diameter using a novel approach in which the local concentration of vasoactive agent was controlled and maintained in vivo. ET-1 and PGF2alpha were applied topically (100 microl every 3 min) to the external surface of the left circumflex coronary artery (LCx) in anesthetized dogs or to the bathing medium of isolated canine LCx rings in parallel in vitro experiments. The dose-dependent constrictions obtained in vivo and in vitro were similar with each agent. Single, approximately maximally effective concentrations of PGF2alpha evoked an initial rapid contraction followed by a slow and sustained larger contraction in both preparations. In contrast, single concentrations of ET-1 elicited a rapid constriction that partially recovered (50-80%) in the ensuing 1.5-2 h despite continuous exposure to ET-1. After the ET-1 constriction reversed, PGF2alpha could still elicit a contraction, indicating a homologous endothelin receptor desensitization. Both agents maximally decreased conduit artery cross-sectional area in vivo by approximately 40% without significantly changing LCx resistance. Thus this in situ technique revealed effects of ET-1 and PGF2alpha on a localized segment of coronary artery that were not discernible with either intravenous or intracoronary administration.

Analysis of Variance↗
PubMed1998

Rabbit polymorphonuclear leukocytes release a factor that causes constriction of the coronary vasculature.

Polymorphonuclear leukocytes (PMN) have been shown to have numerous vasoactive effects, particularly in large artery bioassays. This study shows that rabbit PMN passively release a contractile factor that constricts the coronary vasculature of isolated, Langendorff-perfused rabbit hearts. The mechanism of action of this factor does not involve inhibition of nitric oxide (NO), production of cyclooxygenase metabolites, 5-hydroxytryptamine, or endothelin, or the activation of alpha-adrenoceptors but is a Ca2+-dependent process, because the constriction is inhibited by the Ca2+-channel blocker amlodipine. The activity of this factor is significantly inhibited if it is pretreated with trypsin or heated to 90 degreesC for 10 min, and the active factor is concentrated in the retentate of 100-kDa cutoff centrifuge filters, indicating that the factor is a protein >100 kDa in size. This study shows that rabbit PMN spontaneously release a protein factor that causes constriction of isolated, perfused rabbit hearts by a NO-independent but Ca2+-dependent mechanism.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Transient increases in diameter and [Ca(2+)](i) are not obligatory for myogenic constriction.

Studies were performed to determine the significance of temporal variation in vascular smooth muscle Ca(2+) signaling during acute arteriolar myogenic constriction and, in particular, the importance of the stretch-induced intracellular Ca(2+) concentration ([Ca(2+)](i)) transient in attaining a steady-state mechanical response. Rat cremaster arterioles (diameter approximately 100 microm) were dissected from surrounding tissues, and vessel segments were pressurized in the absence of intraluminal flow. For [Ca(2+)](i) measurements, vessels were loaded with fura 2 and fluorescence emitted by excitation at 340 and 380 nm was measured using video-based image analysis. Ca(2+) and diameter responses were examined after increases in intravascular pressure were applied as an acute step increase or a ramp function. Additional studies examined the effect of longitudinal vessel stretch on [Ca(2+)](i) and arteriolar diameter. Step increase in intraluminal pressure (from 50 to 120 mmHg) caused biphasic change in [Ca(2+)](i) and diameter. [Ca(2+)](i) transiently increased to 114.0 +/- 2.0% of basal levels and subsequently declined to 106.7 +/- 4.4% at steady state. Diameter initially distended to 125.4 +/- 2.1% of basal levels before constricting to 71.1 +/- 1.2%. In contrast, when the same pressure increase was applied as a ramp function (over 5 min) transient vessel distension and transient increase in [Ca(2+)](i) were prevented, yet at steady state vessels constricted to 71.3 +/- 2.5%. Longitudinal stretch resulted in a large [Ca(2+)](i) transient (158 +/- 19% of basal) that returned to baseline despite maintenance of the stretch stimulus. The data demonstrate that the initial vessel distension (reflecting myocyte stretch) and associated global [Ca(2+)](i) transient are not obligatory for myogenic contraction. Thus, although arteriolar smooth muscle cells are responsive to acute stretch, the resulting changes in myogenic tone may be more closely related to other mechanical variables such as wall tension.

Abdominal Muscles↗
PubMed2001

Nitric oxide release during alpha1-adrenoceptor-mediated constriction of arterioles.

We examined endothelial modulation of norepinephrine (NE)-mediated constriction in isolated, cannulated, first-order arterioles from skeletal muscle of rats. Acute arteriolar constrictor responses to NE (10(-9) to 10(-7) M) were significantly (P < 0.05) enhanced after either endothelial denudation or inhibition of nitric oxide synthase with NG-monomethyl-L-arginine (10(-4) M, 30 min). In contrast, arteriolar constrictions to NE were not different after treatment with either the cyclooxygenase inhibitor diclofenac (10(-6) M, 30 min) or the K+-channel blocker tetrabutylammonium (5 x 10(-5) M, 30 min). We also measured arteriolar responses to the vasoconstrictor PGF2alpha; responses were not altered by any of the experimental treatments, which indicates that this phenomenon is not ubiquitous to all vasoconstricting agents. Mechanistically, we examined vascular smooth muscle (VSM) and endothelial cell calcium. Both NE and PGF2alpha significantly increased VSM cell calcium measurements; however, endothelial cell calcium was significantly increased with NE or phenylephrine (an alpha1-adrenergic agonist) but not with PGF2alpha or UK-14304 (an alpha2-adrenergic agonist). Together these findings suggest that in rat cremaster first-order arterioles, NE stimulates an increase in VSM calcium via adrenergic receptors with subsequent increase in endothelial cell calcium, possibly via stimulation of alpha1-adrenergic receptors on the arteriolar endothelium. The burst in endothelial cell calcium may then lead to the production of nitric oxide, which diffuses to the VSM, attenuates constriction, and maintains at least some minimal level of blood flow.

Animals↗
PubMed2006

BK channel beta1-subunit regulation of calcium handling and constriction in tracheal smooth muscle.

The large-conductance, Ca2+-activated K+ (BK) channels are regulators of voltage-dependent Ca2+ entry in many cell types. The BK channel accessory beta1-subunit promotes channel activation in smooth muscle and is required for proper tone in the vasculature and bladder. However, although BK channels have also been implicated in airway smooth muscle function, their regulation by the beta1-subunit has not been investigated. Utilizing the gene-targeted mice for the beta1-subunit gene, we have investigated the role of the beta1-subunit in tracheal smooth muscle. In mice with the beta1-subunit-knockout allele, BK channel activity was significantly reduced in excised tracheal smooth muscle patches and spontaneous BK currents were reduced in whole tracheal smooth muscle cells. Knockout of the beta1-subunit resulted in an increase in resting Ca2+ levels and an increase in the sustained component of Ca2+ influx after cholinergic signaling. Tracheal constriction studies demonstrate that the level of constriction is the same with knockout of the beta1-subunit and BK channel block with paxillin, indicating that BK channels contribute little to airway relaxation in the absence of the beta1-subunit. Utilizing nifedipine, we found that the increased constriction caused by knockout of the beta1-subunit could be accounted for by an increased recruitment of L-type voltage-dependent Ca2+ channels. These results indicate that the beta1-subunit is required in airway smooth muscle for control of voltage-dependent Ca2+ influx during rest and after cholinergic signaling in BK channels.

Animals↗
PubMed2000

Epoxyeicosatrienoic acids constrict isolated pressurized rabbit pulmonary arteries.

Little information is available regarding the vasoactive effects of epoxyeicosatrienoic acids (EETs) in the lung. We demonstrate that 5, 6-, 8,9-, 11,12-, and 14,15-EETs contract pressurized rabbit pulmonary arteries in a concentration-dependent manner. Constriction to 5,6-EET methyl ester or 14,15-EET is blocked by indomethacin or ibuprofen (10(-5) M), SQ-29548, endothelial denuding, or submaximal preconstriction with the thromboxane mimetic U-46619. Constriction of pulmonary artery rings to phenylephrine is blunted by treatment with the epoxygenase inhibitor N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide. Pulmonary arteries and peripheral lung microsomes metabolize arachidonate to products that comigrate on reverse-phrase HPLC with authentic regioisomers of 5,6-, 8,9-, 11,12-, and 14,15-EETs, but no cyclooxygenase products of EETs could be demonstrated. Proteins of the CYP2B, CYP2E, CYP2J, CYP1A, and CYP2C subfamilies are present in pulmonary artery and peripheral lung microsomes. Constriction of isolated rabbit pulmonary arteries to EETs is nonregioselective and depends on intact endothelium and cyclooxygenase, consistent with the formation of a pressor prostanoid compound. These data raise the possibility that EETs may contribute to regulation of pulmonary vascular tone.

8,11,14-Eicosatrienoic Acid↗
PubMed2001

Role of chloride in constriction of descending vasa recta by angiotensin II.

We investigated the dependence of ANG II (10(-8) M)-induced constriction of outer medullary descending vasa recta (OMDVR) on membrane potential (Psim) and chloride ion. ANG II depolarized OMDVR, as measured by fully loading them with the voltage-sensitive dye bis[1,3-dibutylbarbituric acid-(5)] trimethineoxonol [DiBAC(4)(3)] or selectively loading their pericytes. ANG II was also observed to depolarize pericytes from a resting value of -55.6 +/- 2.6 to -26.2 +/- 5.4 mV when measured with gramicidin D-perforated patches. When measured with DiBAC(4)(3) in unstimulated vessels, neither changing extracellular Cl(-) concentration ([Cl(-)]) nor exposure to the chloride channel blocker indanyloxyacetic acid 94 (IAA-94; 30 microM) affected Psim. In contrast, IAA-94 repolarized OMDVR pretreated with ANG II. Neither IAA-94 (30 microM) nor niflumic acid (30 microM, 1 mM) affected the vasoactivity of unstimulated OMDVR, whereas both dilated ANG II-preconstricted vessels. Reduction of extracellular [Cl(-)] from 150 to 30 meq/l enhanced ANG II-induced constriction. Finally, we identified a Cl(-) channel in OMDVR pericytes that is activated by ANG II or by excision into extracellular buffer. We conclude that constriction of OMDVR by ANG II involves pericyte depolarization due, in part, to increased activity of chloride channels.

Angiotensin II↗
PubMed1993

Maintenance of endothelin-induced renal arteriolar constriction in rats is cyclooxygenase dependent.

Influence of arachidonate cyclooxygenase (COX) products on endothelin (ET)-evoked renal vasoconstriction was assessed. In microperfused rat afferent (AA) and efferent arterioles (EA), indomethacin had no effects on the maximal contraction of both AA and EA by ET, but reduced the duration of ET-induced constriction in both arterioles. ET infusion to rats in vivo resulted in a selective increase in efferent but not afferent arteriolar resistance, leading to a dramatic increase in transcapillary hydraulic pressure difference. Glomerular filtration rate (GFR), which fell progressively during infusion of ET alone, was markedly preserved by COX inhibition, but not during selective thromboxane A2 antagonism. In isolated glomeruli, release of prostaglandin (PG) F2 alpha in response to 10(-6) mol/l ET exceeded that the PGE2 by a ratio of 3.2. Collectively, these data provide strong evidence that locally released COX products, possibly PGF2 alpha, play a key role in sustaining ET-induced renal arteriolar constriction. COX inhibition leads to acute vasorelaxation of AA despite continued ET administration, without affecting EA constriction in vivo, thereby resulting in a dramatic reversal of the effects of ET on GFR.

Animals↗
PubMed1996

[Ca2+]i in rat afferent arteriole during constriction measured with confocal fluorescence microscopy.

Using confocal fluorescence microscopy, we followed the time course of intracellular calcium concentration ([Ca2+]i) in vascular smooth muscle cells (VSMC) and endothelial cells (EC) of microperfused afferent arterioles isolated from rat juxtamedullary nephrons. Measurements were made while arterioles were exposed to pharmacological agonists or myogenic stimulation. Luminal addition of acetylcholine triggered an immediate increase of [Ca2+]i in EC and vasodilation. Addition of norepinephrine to the bath solution constricted the vessel and initiated periodic oscillations of [Ca2+]i in VSMC and synchronized vasomotion. Increase of perfusion pressure from 80 to 120 mmHg induced an immediate 9.6 +/- 2.9% (P < 0.05, n = 9) increase of [Ca2+]i in VSMC that was sustained. The arteriole dilated transiently when the perfusion pressure was increased, and persistent vasoconstriction to reduced diameter was observed after 35 s. When nitric oxide (NO) production in the perfused vessel was blocked with nitro-L-arginine methyl ester prior to the pressure step, similar profiles of change in VMSC [Ca2+]i were observed and persistent vasoconstriction began after 28 s. The same pressure step triggered an increase of [Ca2+]i in EC by 11.3 +/- 1.1% (P < 0.05, n = 5). These observations suggest that myogenic constriction of afferent arterioles was associated with an increase of [Ca2+]i in VSMC, and the constriction was delayed by endogenous NO production.

Animals↗
PubMed1997

An Arg-Gly-Asp peptide stimulates constriction in rat afferent arteriole.

The potential role of integrins in the myogenic mechanism was studied in the rat afferent arteriole (AA) by fluorescence immunolocalization and microperfusion of isolated AA. Confocal fluorescence images were acquired from frozen sections of rat kidney after indirect immunostaining for various integrin beta- and alpha-subunits. The beta 1-, beta 3-, alpha 3-, alpha 5-, and alpha V-integrins were found on the plasma membrane in smooth muscle of AA, providing the morphological basis for participation of integrins in mechanotransduction. With 1 mM nitro-L-arginine methyl ester (L-NAME) in the luminal perfusate to inhibit endogenous nitric oxide (NO) production from AA, the hexapeptide GRGDSP (10(-7)-10(-3)M) induced immediate vasoconstriction. The constriction was dose dependent and specific or peptides with arginine-glycine-aspartic acid (RGD) motifs, commonly found on the binding sites of extracellular matrix to integrins. In controls, the hexapeptide GRGESP induced no constriction. GRGDSP, 1 mM, induced a 21.6 +/- 2.6% decrease (P < 0.05, n = 6) in lumen diameter for 30 s and an 18.3 +/- 4.1% increase (P < 0.05, n = 6) in smooth muscle intracellular calcium concentration for 18 s, as measured by the emission ratio of Fluo-3/Fura Red. Binding of exogenous RGD motifs with exposed integrins on AA smooth muscle therefore triggers calcium-dependent vasoconstriction. However, the dose response to RGD was not sensitive to the myogenic tone of the vessel, which suggests that the integrin-mediated vasoconstriction is different from myogenic constriction.

Amino Acid Sequence↗
PubMed1983

Hypoxic constriction of alveolar and extra-alveolar vessels in isolated pig lungs.

To examine whether hypoxia causes constriction of alveolar or extra-alveolar vessels, we determined the relationships among transpulmonary pressure, pulmonary arterial pressure (Ppa), blood flow (Q), and transvascular fluid filtration rate (W) during normoxia (PO2 = 200 Torr) and hypoxia (PO2 = 50 Torr) in isolated pig lungs perfused with autologous blood. Left atrial pressures were always subatmospheric. The effects of lung inflation and hypoxic vasoconstriction on the Ppa-Q relationship were similar; when transpulmonary pressure was greater than 5 Torr, both shifted the curve to higher pressures in a parallel fashion. When transpulmonary pressure was 0-5 Torr, however, inflation had no effect on the Ppa-Q relationship during either normoxia or hypoxia. During normoxia at a transpulmonary pressure of 3.5 Torr, the relationship between fluid filtration rate and flow was characterized by a W of zero at Q less than 1.5 l/min and a rapid increase in W with Q above this value. Both hypoxia and inflation shifted this relationship to higher filtration rates in a parallel fashion. Furthermore, the combined effects of hypoxia and inflation on filtration rate were additive. These results suggest that hypoxia caused constriction of both alveolar and extra-alveolar vessels, resulting in increased intraluminal pressure and filtration of fluid in vessels upstream from the sites of constriction.

Animals↗
PubMed1985

Hypoxia potentiates, oxygen attenuates deflation-induced reflex tracheal constriction.

The reflex tracheomotor responses of in situ isolated segments of the extrathoracic trachea of anesthetized, paralyzed, and ventilated dogs were monitored. Reflex tracheal constriction was evoked by passive lung deflation. The purpose of this study was to determine whether the prevailing state of oxygenation altered the magnitude of this reflex. Compared with the magnitude of the response during normoxia [arterial O2 tension (PaO2) = 78 Torr], that during hypoxia (PaO2 = 44 Torr) was nearly threefold larger while that during hyperoxia (PaO2 greater than 250 Torr) was about 50% smaller. The isocapnic changes in oxygenation by themselves usually had no effect on tracheomotor tone. The deflation-induced reflex tracheal constriction was eliminated by complete denervation of the tracheal segment but usually only diminished by partial denervation. Bilateral vagotomies or bilateral carotid body denervation also usually decreased the magnitude of the reflex. It appears that the magnitude of this reflex is dependent on the prevailing state of oxygenation and that a pulmonary stretch receptor-carotid body chemoreceptor interaction accounts for the exaggerated reflex tracheal constriction during hypoxia and the attenuated response during hyperoxia.

Airway Resistance↗
PubMed1987

Partitioning of pulmonary resistance during constriction in the dog: effects of volume history.

We assessed the relative changes in airways and lung tissue with bronchoconstriction, and the changes in each during and following a deep inhalation (DI). We partitioned pulmonary resistance (RL) into airway (Raw) and tissue (Vtis) components using alveolar capsules in 10 anesthetized, paralyzed, and open-chested dogs ventilated sinusoidally with 350-ml breaths at 1 Hz. We made measurements before and during bronchoconstriction induced by vagal stimulation or inhalation of histamine or prostaglandin F2 alpha (PGF2 alpha), each of which decreased dynamic compliance by approximately 40%. With histamine and PGF2 alpha the rise in RL was predominantly due to Vtis. With vagal stimulation there was a relatively greater increase in Raw than Vtis. At higher lung volumes, Vtis increases offset falls in Raw, producing higher RL at these volumes before and during constriction with PGF2 alpha and histamine. During constriction with vagal stimulation, the fall in Raw with inflation overrode the rise in Vtis, resulting in a lower RL at the higher compared with the lower lung volume. The changes seen after a DI in the control and constricted states were due to alterations in tissue properties, both viscous and elastic. However, the relative hysteresis of the airways and parenchyma were equal, since Raw, our index of airway size, was unchanged after a DI.

Airway Resistance↗
PubMed1992

Tissue viscance during induced constriction in rabbit lungs: morphological-physiological correlations.

Tissue viscance (Vti), the pressure drop across the lung tissues in phase with flow, increases after induced constriction. To gain information about the possible site of response, we induced increases in Vti with methacholine (MCh) and attempted to correlate these changes with alterations in lung morphology. We measured tracheal (Ptr) and alveolar pressure (PA) in open-chest rabbits during mechanical ventilation [frequency = 1 Hz, tidal volume = 5 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O] under control conditions and after administration of saline or MCh (32 or 128 mg/ml) aerosols. We calculated lung elastance (EL), lung resistance (RL), Vti, and airway resistance (Raw) by fitting the equation of motion to changes in Ptr and PA. The lungs were then frozen in situ with liquid nitrogen (PEEP = 5 cmH2O), excised, and processed using freeze substitution techniques. Airway constriction was assessed by measuring the ratio of the airway lumen (A) to the ideally relaxed area (Ar). Tissue distortion was assessed by measuring the mean linear intercept between alveolar walls (Lm), the standard deviation of Lm (SDLm), and an atelectasis index (ATI) derived by calculating the ratio of tissue to air space using computer image analysis. RL, Vti, and EL were significantly increased after MCh, and Raw was unchanged. A/Ar, Lm, SDLm, and ATI all changed significantly with MCh. Log-normalized change (% of baseline) in Vti significantly correlated with A/Ar (r = -0.693), Lm (r = 0.691), SDLm (r = 0.648), and ATI (r = 0.656). Hence, changes in lung tissue mechanics correlated with changes in morphometric indexes of parenchymal distortion and airway constriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1993

Responsiveness of and interactions between airways and tissue in guinea pigs during induced constriction.

Mechanical interdependence between airways and tissues can modify the magnitude of induced bronchoconstriction. We questioned whether the guinea pig, an animal with abundant airway smooth muscle, would differ from other species in the relative responsiveness of and interactions between airways and tissues. Therefore we induced constriction with aerosolized methacholine (MCh) and partitioned responses into airway and tissue components. We measured tracheal and alveolar pressures using alveolar capsules in open-chest guinea pigs (n = 9) during mechanical ventilation [frequency = 1 Hz, tidal volume = 6 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O] and calculated the resistance of lung (RL), tissue (Rti), and airway (Raw) before and after administration of aerosols of MCh in progressively doubling concentrations (0.063-16 mg/ml). In separate animals (n = 10), measurements were made at 3-13 cmH2O PEEP. After aerosols of saline and MCh (0.125-32 mg/ml), measurements were repeated at 3, 7, and 11 cmH2O PEEP. At submaximal levels of constriction, the airways and lung tissues demonstrated similar responsiveness. Increasing PEEP increased RL and Rti and decreased Raw under baseline conditions. At low concentrations of MCh, increasing PEEP increased RL but decreased RL at the highest concentration. Increases in PEEP significantly increased Rti at all concentrations of MCh but decreased Raw only at 8 mg/ml of MCh. These observations demonstrate that, in guinea pigs, during submaximal constriction, airways and tissues behave similarly; moreover, airway-parenchymal interdependence is important in determining the level of bronchoconstriction.

Aerosols↗
PubMed1993

Tissue resistance in the guinea pig at baseline and during methacholine constriction.

Total lung resistance (RL), airway resistance (Raw), and tissue resistance (Rti) were measured in unconstricted and methacholine (MCh)-constricted guinea pigs while tidal volume, lung volume, and breathing frequency were varied. Measurements were made in tracheostomized ventilated guinea pigs with use of alveolar capsules. Relationships between Raw and Rti at different breathing frequencies, lung volumes, tidal volumes, and levels of constriction were compared with previously reported values in other species. Our results demonstrate that, at fixed tidal volume, Rti was inversely related to breathing frequency (Rti approximately f-0.64, where f is breathing frequency in Hz) and increased with increasing lung volume. Rti was a significantly greater percentage of RL after MCh administration (40-50%) than at baseline (15-35%), indicating a greater tissue than airway constrictor response. Rti was also 0.5 log dose more responsive to intravenous MCh than Raw on the basis of the dose required to produce 100% increase in resistance from baseline (PD100). These data show that, in the guinea pig, Rti changes with lung volume, breathing frequency, and constrictor tone in a manner similar to other species previously reported and that Rti can be an important determinant of lung dysfunction during constriction, even in species for which it is small in relation to Raw at baseline.

Airway Resistance↗
PubMed1994

Airway and tissue behavior during induced constriction in rats: intravenous vs. aerosol administration.

The distribution of contractile agonist during intravenous (i.v.) or aerosol (AR) administration is likely to be different. We questioned whether the different pattern of distribution would result in different effects on lung tissue response. We measured tracheal and alveolar pressure in open-chest mechanically ventilated [frequency 1 Hz, tidal volume 8 ml/kg, positive end-expiratory pressure (PEEP) 3 cmH2O] rats under control conditions and after i.v. or AR administration of saline or methacholine (MCh; i.v., 50 micrograms.kg-1.min-1; AR, 256 mg/ml). We calculated lung elastance and resistances of lung, tissue, and airway by fitting the equation of motion to changes in tracheal and alveolar pressure. Lungs were then frozen in situ with liquid nitrogen (PEEP=3 cmH2O) and processed via freeze substitution. Airway constriction was assessed by measuring the ratio of airway lumen to ideally relaxed area. Tissue distortion was assessed by measuring mean linear intercept between alveolar walls (Lm), atelectasis index (ATI) derived by calculating ratio of tissue to air space, and SD of Lm and ATI. I.v. and AR MCh increased lung resistance to a similar degree. However, changes in tissue resistance and lung elastance after AR MCh were significantly greater than those after i.v. MCh, whereas the change in airway resistance was significantly less. After i.v. MCh, airway constriction was prominent and evenly distributed. After AR MCh, airway constriction was less prominent and decreased as airway size decreased. Tissue distortion, i.e., SD of Lm and ATI, was significantly greater after AR than i.v. MCh.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗