Biomedical subjects

B Raffestin

Publications and source records attributed to B Raffestin.

At least 19 recordsLinked to original sources

PubMed1995

Evaluation of an ambulatory device, CID 102, in the diagnosis of obstructive sleep apnoea syndrome.

Diagnosis of obstructive sleep apnoea syndrome (OSAS) is usually performed during overnight polysomnography in the sleep laboratory. In an attempt to simplify the diagnostic strategy, we compared an ambulatory device, CID 102, with polysomnography during the same night in the laboratory in 50 consecutive patients referred for polysomnography. The CID 102 device monitors oxygen saturation, heart rate, body position and tracheal breath sounds. An acoustic pressure sensor is placed on the suprasternal notch. Signals coming from this sensor are amplified and analysed in three different channels, according to their frequency and energy. CID respiratory disturbance index is defined as the number, per hour of analysis time, of apnoeas lasting more than 10 s plus episodes of desaturation by 4% or more associated with pauses lasting from 7-10 s or snores. The polysomnographic data were recorded on paper (Reega 2000, Alvar) and analysed manually. Polysomnographic apnoea-hypopnoea index (AHIp) was defined as the number of apnoeas plus hypopnoeas per hour of sleep. The sensitivity, specificity, positive predictive value and negative predictive value of various CID respiratory disturbance index (> or = 5, > or = 10, > or = 15 and > or = 20 per hour) in diagnosing obstructive sleep apnoea syndrome were determined. When OSAS was diagnosed as AHIp > or = 15, sensitivity and specificity of a CID respiratory disturbance index > or = 5 were 73 and 62%, respectively. Positive predictive value of CID respiratory disturbance index > or = 10 for AHIp > or = 10 was 94%. CID 102 false negative patients had only hypopnoeas without any desaturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Equipment Design↗

PubMed1993

Loss of endothelium-dependent relaxation in proximal pulmonary arteries from rats exposed to chronic hypoxia: effects of in vivo and in vitro supplementation with L-arginine.

To explore endothelium-dependent relaxation and the L-arginine (L-ARG)-nitric oxide (NO) pathway during chronic hypoxia, we examined isolated rings from large conduit pulmonary arteries and aorta from rats exposed to either room air (N), 3-week hypoxia (H), or 3-week H followed by 72-h recovery to normoxia (room air). We examined the vasodilatory actions of acetylcholine (ACh), ionophore A23187, and endothelin-3 (ET-3) on extrapulmonary left and right branches of pulmonary arteries and thoracic aorta precontracted by phenylephrine (PE 10(-6) M). Endothelium-dependent relaxation of N rat pulmonary arteries and aorta to ACh and A23187 was abolished in the presence of L-NG nitroarginine methyl ester (L-NAME 10(-4) M) or methylene blue (MB 10(-5) M) but was suppressed only partially by NG-monomethyl-L-arginine (L-NMMA 5 x 10(-4) M). In pulmonary arteries but not in aorta, ET-3 induced endothelium-dependent relaxation that was suppressed by L-NAME, MB, and L-NMMA. Pulmonary arteries from H rats did not relax with ET-3. As compared with those of N rats, they exhibited less relaxation to ACh and A23187, (47 +/- 3 vs. 89 +/- 2 and 53 +/- 2 vs. 85 +/- 4%, p < 0.001, respectively) but exhibited similar relaxation to the nonendothelium-dependent vasodilator linsidomine. In contrast, endothelial-relaxation did not differ between N and H rat aorta.2+ pretreatment with L-ARG.

Acetylcholine↗

PubMed1992

L-arginine restores endothelium-dependent relaxation in pulmonary circulation of chronically hypoxic rats.

We investigated whether loss of endothelial-derived relaxing factor (EDRF) activity in the pulmonary vessels of chronically hypoxic rats could be restored by pretreatment with L-arginine. We measured vasodilation to acetylcholine (ACh), calcium ionophore A23187, or linsidomine (Sin-1) under conditions of increased vascular tone induced by U-46619 (50 pmol/min), as well as vasoconstriction to endothelin-1 (ET) in isolated lungs pretreated with meclofenamate (3 microM). In lungs from normoxic (N) rats, in vitro L- or D-arginine (10(-3) M) did not alter vasodilation to the endothelium-dependent agents ACh (10(-9)-10(-6) M) and A23187 (10(-9)-10(-7) M), but NG-monomethyl-L-arginine (10(-3) M) completely abolished it. In lungs from rats exposed to 3 wk of hypoxia (H), vasodilation to ACh or A23187 was fully restored after in vitro L-arginine (10(-3) M) or N alpha-benzoyl-L-arginine (5 x 10(-5) M) but remained abolished after D-arginine, L-citrulline, L-ornithine, or L-argininosuccinic acid. In vivo pretreatment of H rats with L-arginine (300 mg/kg iv) 30 min before isolating the lung also restored vasodilation to A23187. Vasodilation to the endothelium-independent agent Sin-1 was similar in both groups of lungs and was not altered by in vitro L-arginine. L-arginine attenuated the increased pressor response to ET (300 pmol) of H rat lungs but had no effect in N rats. Our results demonstrate that loss of EDRF activity associated with hypoxic pulmonary hypertension may be reversed by supplying L-arginine.

Acetylcholine↗

PubMed1992

Pulmonary vasodilatory action of endogenous atrial natriuretic factor in rats with hypoxic pulmonary hypertension. Effects of monoclonal atrial natriuretic factor antibody.

We administered ascitic fluid containing atrial natriuretic factor (ANF) monoclonal antibody to rats after 3 weeks of exposure to hypoxia while the rats were still hypoxic. In additional chronically hypoxic rats, we infused synthetic rat ANF. In conscious chronically instrumented rats, after a bolus dose of 5 micrograms i.v. ANF, pulmonary arterial pressure fell significantly from 26.5 +/- 2 to 21 +/- 2 mm Hg (p less than 0.01), reaching its nadir at 5 minutes without change of systemic arterial pressure, cardiac output, or heart rate. Pulmonary arterial pressure increased gradually from 26 +/- 4 to 34 +/- 4 mm Hg within 30 minutes (p less than 0.05) after acute administration of ANF monoclonal antibody and decreased transiently to return to baseline within 15 minutes after infusion of control ascitic fluid containing monoclonal antibody against an apolipoprotein. Cardiac output and heart rate remained unchanged after both ANF monoclonal antibody and control ascitic fluid. In normoxic rats, acute administration of ANF monoclonal antibody did not cause significant changes in pulmonary arterial pressure, cardiac output, or heart rate. Rats receiving weekly intravenous injections of ANF monoclonal antibody that were started before initiation of exposure to hypoxia experienced significantly aggravated pulmonary hypertension and right ventricular hypertrophy compared with rats receiving repeated infusions of control ascitic fluid. However, there was no significant difference in small pulmonary arterial wall thickness or percentage of muscularized arteries at the alveolar duct level. These results suggest that endogenous ANF attenuates hypoxic pulmonary hypertension by decreasing pulmonary vascular tone.

Animals↗

PubMed1991

Pulmonary vascular reactivity to endothelin-1 in normal and chronically pulmonary hypertensive rats.

The pulmonary vascular reactivity to endothelin-1 (ET-1) was assessed in rats previously exposed to 11% O2 (hypoxic) or room air (controls) for 3 weeks. In isolated control lung preparations studied during conditions of increased tone by U46619 (50 pmol/min) and treated with meclofenamate (3 microM), low doses of ET-1 (30 and 100 pM) reduced the pressor response to U46619 by 58 +/- 5% (p less than 0.01). Vasodilation induced by ET-1 was not abolished by the antagonist of endothelium-dependent relaxing factor (EDRF) NG-monomethyl-L-arginine (5 x 10(-4) M), which suppressed vasodilator response to ionophore A23187 (10(-8)-10(-7) M). Higher doses of ET-1 (300 and 1,000 pM) induced vasoconstriction during conditions of basal tone, and the pressor response to 300 pM ET-1 was enhanced by EDRF antagonists. Administration of ET-1 to lungs from hypoxic rats failed to cause pulmonary vasodilation and instead induced a greater pulmonary pressor response (300 pM) than in control rat lungs (7 +/- 1.5 vs. 1.6 +/- 0.5 mm Hg, p less than 0.01), which was not further potentiated by EDRF antagonists. Infusion of 300 pM ET to conscious catheterized animals induced a sustained increase in pulmonary resistance only in the hypoxic group (from 305 +/- 37 to 389 +/- 55 mm Hg/L/min, p less than 0.01) (n = 7). The results suggest that depending on the dose, ET-1 can cause pulmonary vasodilation (independent of EDRF release) or vasoconstriction (opposed by EDRF). During chronic hypoxic pulmonary hypertension, ET-1 behaves only as a pulmonary vasoconstrictor.

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

PubMed1991

Pulmonary vascular response to endothelin in rats.

This study investigated the pulmonary vascular response to endothelin (ET) in rats. In conscious rats, an incremental intravenous bolus of ET-1 (100-1,000 pM) caused, after an initial drop in systemic arterial pressure (Psa), a secondary dose-dependent increase of Psa concomitant with a decrease of cardiac output (CO) and heart rate (HR). Pulmonary arterial pressure (Ppa) remained unchanged, and pulmonary vascular resistance (PVR) increased significantly only after 1,000 pM (+ 40.0 +/- 10.4 at 15 min). Meclofenamate (6 mg/kg iv) did not alter hemodynamic response to ET (300 pM). After autonomic blockade with hexamethonium (6 mg/kg iv) plus atropine (0.75 mg/kg iv), bradycardia response to ET (300 pM) was blocked, but CO decreased, systemic vascular resistance increased, and PVR remained unchanged as in controls. In anesthetized ventilated rats, bolus injections of ET (10-1,000 pM) induced a transient dose-related decrease in compliance (-10.9 +/- 1.8% after 1,000 pM) but no change of conductance. In isolated lungs, Ppa increased at doses greater than 100 pM, and edema developed in response to 1,000 pM ET. The rise of Ppa in response to 300 pM was not altered by meclofenamate (3.2 x 10(-6) M) but was potentiated by inhibitors of endothelium-derived relaxing factor(s) (EDRF), methylene blue (10(-4) M), pyrogallol (3 x 10(-5) M), and NG-monomethyl-L-arginine (6 x 10(-4) M) (3.9 +/- 0.3, 4.6 +/- 0.5, and 5.9 +/- 0.3 mmHg, respectively, compared with 1.5 +/- 0.5 mmHg in control lungs). These results suggest that circulating ET is a more potent constrictor of the systemic circulation than of the pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Loss of endothelium-dependent relaxant activity in the pulmonary circulation of rats exposed to chronic hypoxia.

To determine whether exposure to chronic hypoxia and subsequent development of pulmonary hypertension induces alterations of endothelium-dependent relaxation in rat pulmonary vascular bed, we studied isolated lung preparations from rats exposed to either room air (controls) or hypoxia (H) during 1 wk (1W-H), 3 wk (3W-H), or 3W-H followed by 48 h recovery to room air (3WH + R). In lungs pretreated with meclofenamate (3 microM), the endothelium-dependent vasodilator responses to acetylcholine (10(-9)-10(-6) M) and ionophore A23187 (10(-9)-10(-7) M) were examined during conditions of increased tone by U46619 (50 pmol/min). Acetylcholine or A23187 produced dose-dependent vasodilation in control lungs, this response was reduced in group 1W-H (P less than 0.02), abolished in group 3W-H (P less than 0.001), and restored in group 3WH + R. In contrast, the endothelium-independent vasodilator agent sodium nitroprusside remained fully active in group 3W-H. The pressor response to 300 pM endothelin was greater in group 3W-H than in controls (6.8 +/- 0.5 mmHg vs. 1.6 +/- 0.2 mmHg, P less than 0.001) but was not potentiated by the endothelium-dependent relaxing factor (EDRF) antagonists: hydroquinone (10(-4) M); methylene blue (10(-4) M); and pyrogallol (3 x 10(-5) M) as it was in controls. It was similar to controls in group 3W-H + R. Our results demonstrate that hypoxia-induced pulmonary hypertension is associated with a loss of EDRF activity in pulmonary vessels, with a rapid recovery on return to a normoxic environment.

Acetylcholine↗

PubMed1990

Synthesis and secretion of atrial natriuretic factor during chronic hypoxia: a study in the conscious instrumented rat.

1. To investigate the mechanisms leading to enhanced synthesis and release of atrial natriuretic factor during chronic hypoxia, we measured immunoreactive plasma atrial natriuretic factor, blood gases, packed cell volume, pulmonary artery pressure and systemic artery pressure in male Sprague-Dawley rats exposed to 1, 2 or 3 weeks of normobaric hypoxia. Rats were implanted with pulmonary and carotid artery catheters and studied conscious, 23 h after return to hypoxia. 2. The concentration of atrial natriuretic factor messenger RNA was measured in the right and left ventricular free walls of rats exposed to 3 weeks of hypoxia and in normoxic control rats. 3. There was a trend for plasma atrial natriuretic factor to increase with the duration of exposure to hypoxia but only the 3-week hypoxic rats had a significantly higher level (1080 +/- 193 pg/ml) than the normoxic control rats (318 +/- 46 pg/ml, P less than 0.05, mean +/- SEM). When all the data from normoxic and hypoxic rats were considered together, plasma atrial natriuretic factor was positively correlated with packed cell volume (r = 0.66, P less than 0.001), pulmonary artery pressure (r = 0.68, P less than 0.002), and the index of right ventricular hypertrophy (r = 0.54, P less than 0.01), but after analysis of partial correlation, packed cell volume was the only independent contributing factor to the variance in the level of plasma atrial natriuretic factor (r2 = 0.24).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Protein kinase C influences rat pulmonary vascular reactivity.

To test the role of protein kinase C in the control of pulmonary vascular tone and reactivity, we examined the effects of the activators, phorbol 12-myristate-13-acetate (PMA), mezerein, and 1,2-dioctanyl-rac-glycerol (1,2-DOG), in rat isolated large pulmonary arteries and salt solution-perfused lungs. PMA (500 nM) and mezerein (100 nM) induced slow, sustained contractions of isolated pulmonary arteries. These contractions were not inhibited by nifedipine (1 microM), the intracellular Ca2+ blocker TMB-8 (50 microM), a 0 Ca2+ and EGTA (2 mM) bath, or endothelial denudation. They were reduced by amiloride (500 microM), an inhibitor of Na+/H+ exchange, and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7); (50 microM), an inhibitor of protein kinase C. PMA caused concentration-dependent (5 to 500 nM) potentiation of KCl, serotonin, and A23187 contractions of isolated pulmonary arteries. The effect of PMA on norepinephrine contraction was dependent on both concentration and time. Whereas PMA potentiated norepinephrine contraction after 5 min, it inhibited the response after 60 min. PMA and mezerein also caused concentration-dependent (0.5 to 500 nM) vasoconstriction in isolated lungs. The PMA vasoconstriction was unaltered by meclofenamate (1.6 microM) but was attenuated by nifedipine (1 microM). Low concentrations of PMA (5 nM) and 1,2-DOG (50 microM) potentiated both hypoxic and KCl vasoconstriction in isolated lungs. In contrast, the hypoxic and KCl responses were blunted by H-7 (30 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Human isolated bronchial muscle preparations from asthmatic patients: effects of indomethacin and contractile agonists.

Airway reactivity to histamine was determined in a group of non-asthmatic and asthmatic patients prior to thoracotomy. The latter group was more reactive to histamine provocation than the former (PC40: 28.40 +/- 6.27 mg/ml and 1.15 +/- 0.19 mg/ml, respectively). Subsequent to the surgical intervention, isolated human bronchial muscle preparations were obtained from both groups (15 non-asthmatic and 5 asthmatic subjects). Histamine concentration-effect curves were generated both in the absence and in the presence of indomethacin (1.7 microM; 30 min). Neither the basal tone nor the histamine response and sensitivity of the preparations were altered by the antiinflammatory drug. In bronchial preparations from one asthmatic subject, indomethacin significantly reduced the prostaglandin production during histamine contraction. Prostaglandin E2 and F2 alpha contracted isolated human bronchial muscle preparations from these asthmatic individuals. These data suggest that endogenous prostaglandins may not regulate the contractile response to histamine in vitro.

Acetylcholine↗

PubMed1989

Effects of thiazinamium chloride on human isolated bronchial muscle preparations.

In human bronchial muscle preparations contracted with histamine, the rank order potency for the relaxant effect of various antagonists was: thiazinamium chloride less than tripelennamine less than atropine (pD2 values: 7.78, 6.16 and greater than 4 for each antagonist, respectively). These antagonists also relaxed human isolated bronchial muscle preparations contracted with acetylcholine. The rank order potency was: atropine less than thiazinamium chloride less than tripelennamine (pD2 values: 7.76, 6.94 and 4.05, respectively). Tripelennamine and thiazinamium chloride displaced histamine concentration-effect curves and atropine and thiazinamium chloride antagonized acetylcholine curves in human isolated bronchial muscle preparations. These results suggest that thiazinamium chloride may have important therapeutic value in airways disease since this drug not only relaxed human isolated airway muscle preparations but also antagonized contractile responses in these tissues to both histamine and acetylcholine.

Atropine↗

PubMed1987

Effects of various pharmacological agents on isolated human bronchial and pulmonary arterial and venous muscle preparations contracted by leukotriene D4.

The response of isolated human bronchial muscle preparations to leukotriene D4 (LTD4, 0.1 microM; 0.22 +/- 0.03 g/mm2) was similar to that of histamine (50 microM; 0.21 +/- 0.02 g/mm2). Isolated pulmonary venous preparations also contracted to these same concentrations of both agonists (LTD4, 0.32 +/- 0.19 g/mm2; and histamine, 0.36 +/- 0.07 g/mm2). However, pulmonary arterial preparations responded to histamine (50 microM, 0.59 +/- 0.10 g/mm2) but exhibited a reduced response to LTD4 (0.3 microM, 0.06 +/- 0.01 g/mm2). Bronchial and pulmonary venous muscle preparations from the human lung had the same sensitivities to LTD4 (pD2 values: bronchus, 7.95 +/- 0.08 and vein, 7.76 +/- 0.07). When bronchial or pulmonary venous muscle preparations were incubated for 30 min with either diltiazem (10 microM), indomethacin (1.7 microM) or L-cysteine (3 microM), the LTD4 cumulative concentration-effect curves following these drug treatments were similar to controls. However, FPL-55712 (10 microM) significantly shifted the LTD4 concentration-effect curves produced in bronchial preparations to the right. In isolated pulmonary arterial preparations none of these drug treatments enhanced the LTD4 response. These results show that isolated human pulmonary arterial preparations are less responsive to LTD4 than bronchial or venous preparations. In addition, the data obtained subsequent to the various drug treatments indirectly suggest that the LTD4 contraction is not modified by a calcium channel blocker or by inhibition of the endogenous products of the cyclooxygenase pathway.

Arteries↗

PubMed1987

Effects of intracellular pH on hypoxic vasoconstriction in rat lungs.

Isolated rat lungs perfused with physiological salt-Ficoll solutions were studied to test whether hypoxic pulmonary vasoconstriction was potentiated by increases in intracellular pH (pHi) and blunted by decreases in pHi. Whereas addition to perfusate of 5 nM phorbol myristate acetate (PMA), a stimulator of exchange of intracellular H+ for extracellular Na+, potentiated hypoxic vasoconstriction, 1 mM amiloride, an inhibitor of Na+-H+ exchange, blunted the hypoxic response. Hypoxic vasoconstriction was also potentiated by the weak bases NH4Cl (20 mM), methylamine (10 mM), and imidazole (5 mM) and was inhibited by the weak acid sodium acetate (40 mM). NH4Cl, imidazole, and acetate had the same effects on KCl-induced vasoconstriction and on the hypoxic response. Hypoxic vasoconstriction was greater in lungs perfused with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered solution than in those perfused with CO2/HCO3--buffered solution. Similarly, lungs perfused with CO2/HCO3--buffered solution containing 1.8 mM Cl- (NaNO3 and KNO3 substituted for NaCl and KCl) had larger hypoxic and angiotensin II pressor responses than those perfused with 122.5 mM Cl-. Because PMA, NH4Cl, methylamine, imidazole, HEPES-buffered solutions, and low-Cl- solutions can cause increases in pHi and amiloride and acetate can cause decreases in pHi, these results suggest that intracellular alkalosis and acidosis, respectively, potentiate and blunt vasoconstrictor responses to hypoxia and other stimuli in isolated rat lungs. These effects could be related to pHi-dependent changes in either the sensitivity of the arterial smooth muscle contractile machinery to Ca2+ or the release of a vasoactive mediator or modulator by some other lung cell.

Acetates↗

PubMed1986

Time course of muscular blood metabolites during forearm rhythmic exercise in hypoxia.

O2 concentration, PO2, PCO2, pH, osmolarity, lactate (LA), and hemoglobin (Hb) concentrations in deep forearm venous blood were repeatedly measured during submaximal exercise of forearm muscles. Concentrations of arterial blood gases were determined at rest and during exercise. Experiments were conducted under normoxia and hypobaric hypoxia (PB = 465 Torr). In arterial blood, data obtained during exercise were the same as those obtained during rest under either normoxia or hypoxia. In venous muscular blood, PO2 and O2 concentration were lower at rest and during exercise in hypoxia. The muscular arteriovenous O2 difference during exercise in hypoxia was increased by no more than 10% compared with normoxia, which implied that muscular blood flow during exercise also increased by the same percentage, if we assume that exercise O2 consumption was not affected by hypoxia. Despite increased [LA], the magnitude of changes in PCO2 and pH in hypoxia were smaller than in normoxia during exercise and recovery; this finding is probably due to the increased blood buffer value induced by the greater amount of reduced Hb in hypoxia. Hence all the changes occurring in hypoxia showed that local metabolism was less affected than we expected from the decrease in arterial PO2. The rise in [Hb] that occurred during exercise was lower in hypoxia. Possible underlying mechanisms of the [Hb] rise during exercise are discussed.

Adult↗

PubMed1986

Comparison of human bronchial muscle responses to histamine in vivo with histamine and isoproterenol agonists in vitro.

In an effort to explain the large variation of airway reactivity to histamine in human subjects in vivo, we have examined the relationship between histamine responses in vivo and isoproterenol in vitro. The bronchial reactivity in patients with lung carcinoma was assessed prior to surgery by measuring the provocative concentration of histamine that resulted in a 20 or a 40% reduction in either forced expiratory volume in one second or specific airway conductance (SGaw). We also determined the pD2 value (-Log EC50 molar) to histamine and isoproterenol in isolated bronchial muscle preparations from these subjects. A wide range of histamine responsiveness was observed in vivo for the 17 patients (PC40 SGaw: 1.3 to greater than 64 mg/ml of histamine). There was no correlation between this latter parameter and the bronchial histamine sensitivity in vitro. However, isolated bronchial muscle preparations from asthmatic subjects were less sensitive to isoproterenol than were those preparations from nonasthmatic subjects.

Adult↗

PubMed1986

Cardiopulmonary effects of a single oral dose of almitrine at rest and on exercise in patients with hypoxic chronic airflow obstruction.

Almitrine, a new triazine derivative, was studied in a double-blind, randomized, parallel study in 16 patients with hypoxic chronic airflow obstruction (eight almitrine and eight placebo). At rest, compared to placebo, a 3 mg/kg single dose of almitrine given orally significantly increased the partial pressure of oxygen (mean increase: +12.0 +/- SEM 2.1 mm Hg, p less than 0.001) and decreased the partial pressure of carbon dioxide (mean decrease: -6.0 +/- 0.7 mm Hg, p less than 0.001); this improvement in arterial blood gases persisted on exercise. The lack of significant change in ventilation and the decrease in the alveolar-arterial oxygen gradient (mean decrease -10.0 +/- 1.9 mm Hg; p less than 0.001) at rest suggests a change in the distribution of the ventilation-perfusion ratio in the lung; such a change was confirmed by a krypton 81m isotopic study. Pulmonary hemodynamic responses were studied at rest and on exercise; a significant but slight increase in mean pulmonary artery pressure at rest (+4.0 +/- 1.5 mm Hg, p less than 0.05) was found.

Administration, Oral↗

PubMed1986

Histamine contraction of isolated human airway muscle preparations: role of prostaglandins.

Histamine concentration-effect curves were obtained using either an individual or cumulative dosing method. The maximal response to histamine in bronchial preparations using the individual dosing protocol was 0.25 +/- 0.03 g/mm2 and similar results were obtained using the cumulative method (0.24 +/- 0.03 g/mm2). The sensitivity (pD2 value) of isolated human bronchial muscle preparations was comparable for both the individual and cumulative methods (5.71 and 5.16, respectively). Prostaglandin (PG) E2 and PGF2 alpha contracted isolated human bronchial muscle preparations and the pD2 values were 5.64 and 5.59, respectively. PGE2 did not relax bronchial muscle preparations contracted with histamine (50 microM). At high concentrations prostacyclin (3 microM) relaxed histamine-contracted bronchial tissues but this effect was quite variable. Indomethacin (1.7 microM) did not affect basal tone in bronchial tissues. Isolated human bronchial preparations which were contracted maximally with histamine always released measurable quantities of PGs. In some experiments the rat stomach strip was used to detect the presence of these substances before and subsequent to the indomethacin (1.7 microM) treatment. The use of radioimmunoassay for PGE2 and PGF2 alpha confirmed these bioassay results. In a large number of experiments (18 preparations from 9 individual lung samples) the baseline production of PGs was PGE2, 22.9 +/- 2.8 pg/mg of tissue and PGF2 alpha, 11.9 +/- 2.5 pg/mg of tissue. Subsequent to histamine stimulation the quantities of PGs released were PGE2, 72.4 +/- 7.6 pg/mg of tissue and PGF2 alpha, 40.9 +/- 7.3 pg/mg of tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗

PubMed1985

Response and sensitivity of guinea-pig airway muscle preparations to 5-hydroxytryptamine during ontogenesis.

Responsiveness (g mm-2) and sensitivity (pD2 value) to 5-hydroxytryptamine (5-HT) were markedly reduced in isolated tracheal and bronchial tissues from guinea-pigs during ontogenesis. Responsiveness of the trachea to 5-HT was depressed much more than that to histamine. Airway preparations from young guinea-pigs of either sex always contracted when exposed to 5-HT, an effect that was blocked by methysergide. Airway muscle preparations from old animals exhibited a wide range of responses to 5-HT, namely, no effect, relaxation or contraction. The contractile effect of 5-HT in tracheal and bronchial preparations from old animals was always blocked by methysergide, whereas, the relaxant effect was not. These results indicate that there are significant alterations in the response to 5-HT receptor stimulation in airway muscle preparations from guinea-pigs during ontogenesis.

Aging↗