Ontogeny of epithelial modulation of airway smooth muscle function in the guinea pig

Southgate, W. Michael; Pichoff, B. E.; Stevens, Edward L.; Balaraman, Venkataraman; Uyehara, Catherine F. T.; Nakamura, Kenneth T.

doi:10.1002/ppul.1950150207

Cited by 13 publications

(4 citation statements)

References 22 publications

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“…Conceivably, during development, differences between species may be determined by influences exerted on force production by nonmuscle tissue, e.g., the epithelium. The removal of the epithelium did not alter force production in an in situ swine tracheal preparation (14), but it abolished maturational differences in guinea pigs (24). Moreover, our laboratory (13) has recently observed in guinea pigs an age-related increase in epithelial secretion of inhibitory PGE 2 accompanied by decreases in contractile thromboxane B 2 and leukotriene C 4 .…”

Section: Discussionmentioning

confidence: 85%

Different ontogeny of rate of force generation and shortening velocity in guinea pig trachealis

Chitano

Wang

Cox

et al. 2000

Journal of Applied Physiology

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Juveniles of many species, including humans, display greater airway responsiveness than do adults. This may involve changes in airway smooth muscle function. In the present work we studied force production and shortening velocity in trachealis from 1-wk-old (1 wk), 3-wk-old (3 wk), and 3-mo-old (adult) guinea pigs. Strips were electrically stimulated (60 Hz, 18 V) at their optimal length (l(o)) to obtain maximum active stress (P(o)) and rate of stress generation. Then, force-velocity curves were elicited at 2.5 s from the onset of the stimulus. By applying a recently developed modification of Hill's equation for airway smooth muscle, the maximum shortening velocity at zero load (V(o)) and the value alpha. gamma/beta, an index of internal resistance to shortening (Rsi), were calculated (alpha, beta, and gamma are the constants of the equation). P(o) increased little with maturation, whereas the rate of stress generation increased significantly (0.40 +/- 0.03, 0.45 +/- 0.03, 0. 51 +/- 0.03 P(o)/s for 1 wk, 3 wk, and adult animals). V(o) slightly increased early with maturation to decrease significantly later (1. 79 +/- 0.67, 2.45 +/- 0.92, and 0.55 +/- 0.09 l(o)/s for 1 wk, 3 wk, and adult animals), whereas the Rsi showed an opposite trend (14.98 +/- 5.19, 8.99 +/- 3.01, and 32.07 +/- 5.54 mN. mm(-2). l(o)(-1). s for 1 wk, 3 wk, and adult animals). This early increase of force generation in combination with late increase of Rsi may explain the changes of V(o) with age. An elevated V(o) may contribute to the incidence of airway hyperresponsiveness in healthy juveniles.

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Section: Discussionmentioning

confidence: 85%

Different ontogeny of rate of force generation and shortening velocity in guinea pig trachealis

Chitano

Wang

Cox

et al. 2000

Journal of Applied Physiology

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“…ORT of rings of extrathoracic trachea, mainstem bronchus, aorta, and pulmonary artery were determined as previously described (15,20,25) except that a higher concentration of norepinephrine (6 X 10W6 M) was used for vascular tissues. ORT is the tension due to passive stretch at which each ring responds maximally to a constrictor.…”

Section: Methodsmentioning

confidence: 99%

Acute Hyperoxic Injury Attenuates the Relaxing Effects of “Loop” Diuretics and Salbutamol on Large Airways of Newborn Guinea Pigs

et al. 1995

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We have previously found an age-dependent relaxing effect of furosemide in normal fetal, newborn, and adult guinea pig airways with fetal trachea exhibiting the greatest relaxation and adult tissue the least. This study was designed to expand upon this finding by determining if in vivo hyperoxic exposure would influence in vitro airway relaxation mediated by the loop diuretics, furosemide and ethacrynic acid, and the P2-adrenoceptor agonist, salbutamol. Newborn guinea pigs were raised in >95% FiO, until ill; controls in room air. Isometric relaxation to 3 X lop5 M furosemide, 3 X 10-% ethacrynic acid, or 1 0~' -1 0~" M salbutamol was recorded in 3 X lop" M histamine-constricted airway rings. Ethacrynic acid, like furosemide, relaxed newborn Recent evidence suggests that furosemide modulates airway reactivity in vivo. Inhaled furosemide attenuates exercise-(I), allergen-(2), and cold air-(3, 4) induced bronchoconstriction in asthmatic adults, and cold air-induced bronchospasm in asthmatic children (5). Furthermore, systemic furosemide decreases airway resistance in infants with bronchopulmonary dysplasia (6-10). Although the mechanisms of furosemide's pulmonary effects have yet to be fully established, most researchers conclude that these effects are unrelated to diuresis. Various mechanisms have been espoused, including inhibition of pulmonary nerves ( l l ) , increased pulmonary venous capacitance (12), increased efferent pulmonary lymph flow (13) Medical Center; University of Hawaii Leahi Trust; and National Institutes of Health Grant guinea pig airways. Hyperoxia did not alter the contractile effect of 3 X 1 0 -M histamine but did significantly decrease the relaxing effect of furosemide, ethacrynic acid, and salbutamol. Loop diuretic mediated airway relaxation was accentuated in HEPES buffer when compared with Krebs, whereas salbutamolmediated relaxation was unaffected. These results suggest that hyperoxia nonspecifically decreases airway responsiveness to the relaxing agents studied. (Pediatr Res 38: 280-285, 1995) Abbreviations ORT, optimal resting tension FiO,, fraction of inspired oxygen increased oncotic pressure leading to decreased efferent pulmonary transcapillary flow (12,14). Stevens et al. (15) found that furosemide directly relaxes normal isolated guinea pig airways, suggesting another possible mechanism.Furosemide, bumetanide, and ethacrynic acid bind to a Na+-K+-Cl-cotransporter in the thick ascending loop of Henle (16,17). This transporter is also functional in other tissues (18). The possible role of this cotransporter in vascular smooth muscle function was first hypothesized by Deth and coworkers (19) who found evidence for a functional Na+-K+-C1-cotransporter in vascular smooth muscle by demonstrating that: 1) '%b uptake (a marker for Kt transport) is inhibited by furosemide in the presence of ouabain (to inhibit Na-KATPase) and is ~a + -, K+-, and C1--(substrate) dependent; and 2) uptake of 4 5~a in rat aorta is reduced by furosemide. They further suggest that HEPES buffer increases...

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“…Epithelium was denuded by gentle rubbing with a wooden probe [19] to remove epithelial ion channels. Ring segments were incubated with either furosemide (300 ÌM, 1 h) or salbutamol (10 ÌM, 30 min).…”

Section: Rb Uptakementioning

confidence: 99%

Cross-Desensitization to Furosemide and Salbutamol in Isolated Neonatal Guinea Pig Airways

Gelber

Christ²,

Iwamoto

et al. 1999

Neonatology

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Airway hyperresponsiveness in neonatal chronic lung disease is treated with both furosemide, a diurectic that inhibits the Na-K-2Cl cotrasporter, and salbutamol, a β₂-adrenoceptor agonist. Tachyphylaxis to both drugs in vitro has been described. This study was conducted to determine if the relaxation response in newborn guinea pig airways to furosemide and salbutamol can be cross-desensitized in vitro. Tracheal ring segments from 4- to 7-day-old guinea pigs were suspended in HEPES buffer for measurement of isometric tension. Segments were pre-treated with either furosemide (300 μM, 1 h) or salbutamol (10 μM, 30 min). After constriction with 3 μM acetylcholine, relaxation response to salbutamol or furosemide, respectively, was measured. Pretreatment with furosemide diminished relaxation response to salbutamol [87 ± 3% (n = 11) vs. 117 ± 8% (n = 10), p < 0.05], as compared to saline-treated controls. In addition, pretreatment with salbutamol diminished relaxation response to furosemide [53 ± 2% (n = 11) vs. saline-treated (83 ± 7%, n = 7, p < 0.05) and DMSO-treated controls (69 ± 5%, n = 5, p < 0.05)]. Measurements of ⁸⁶Rb uptake, cyclic AMP levels and responses in the presence of charybdotoxin make it unlikely that Na-K-2Cl cotransporter activity, stimulation of cAMP, or opening of maxi-K⁺ channels are mechanisms involved in the cross-desensitization to furosemide and salbutamol in vitro.

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Ontogeny of epithelial modulation of airway smooth muscle function in the guinea pig

Cited by 13 publications

References 22 publications

Different ontogeny of rate of force generation and shortening velocity in guinea pig trachealis

Different ontogeny of rate of force generation and shortening velocity in guinea pig trachealis

Acute Hyperoxic Injury Attenuates the Relaxing Effects of “Loop” Diuretics and Salbutamol on Large Airways of Newborn Guinea Pigs

Cross-Desensitization to Furosemide and Salbutamol in Isolated Neonatal Guinea Pig Airways

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