We tested the hypothesis that hyperpnea-induced bronchoconstriction (HIB) and hyperpnea-induced bronchovascular hyperpermeability (HIBVH) are mediated through stimulation of NK-1 and NK-2 receptors in guinea pigs. We first established the efficacy and selectivity of (+/-) CP-96,345 (3 mg/kg i.v.) and of SR-48,968 (300 micrograms/kg i.v.) as NK-1 and NK-2 antagonists, respectively. (+/-) CP-96,345 substantially attenuated bronchoconstriction and systemic vascular leak caused by administration of Sar9,Met(O2)11-Substance P (a specific NK-1 agonist), but had no effect upon bronchoconstriction induced by selective NK-2 stimulation with Nle10-Neurokinin A[4-10]. Conversely, SR-48,968 antagonized the bronchoconstrictor response to Nle10-NKA[4-10], right-shifting the dose-response curve by 2 log units, but had no effect on Sar9, Met(O2)11-SP-induced bronchoconstriction. Anesthetized, tracheostomized, opened-chest male Hartley guinea pigs were pretreated with (+/-) CP-96,345 (3 mg/kg i.v.), SR-48,968 (300 micrograms/kg i.v.), or their respective vehicles, and Evans blue dye (30 mg/kg i.v.) to label circulating albumin. 10 min isocapnic dry gas hyperpnea (12 ml/kg, 150 breaths/min) provoked HIB and HIBVH in vehicle-treated animals. (+/-) CP-96,345 reduced the magnitude of HIB by one-half (peak posthyperpnea RL 7.8 +/- 1.9 [SE] times prehyperpnea baseline versus 16.1 +/- 2.6, vehicle-treated; P < or = 0.0001, ANOVA); SR-48,968 blocked HIB more completely (peak posthyperpnea RL 5.1 +/- 1.7 [SE] times prehyperpnea baseline versus 19.3 +/- 2.8, vehicle-treated; P < 0.0001, ANOVA). Neither drug reduced HIBVH. We conclude that dry gas hyperpnea causes bronchoconstriction in guinea pigs through activation of tachykinin receptors. The differential effects of neurokinin receptor blockade on HIB and HIBVH demonstrate that hyperpnea-induced airflow obstruction is not primarily a consequence of hyperpnea-induced bronchovascular leak.
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http://dx.doi.org/10.1172/JCI116569 | DOI Listing |
Int J Nanomedicine
January 2025
College of Animal Science, Guizhou University, Guiyang, Guizhou, People's Republic of China.
Background: Adjusting thickening agent proportions in nanoemulsion gel (NG) balances its transdermal and topical delivery properties, making it more effective for dermatophytosis treatment.
Methods: Carbomer 940 and α-pinene were used as model thickening agent and antifungal, respectively. A series of α-pinene NGs (αNG1, αNG2, αNG3) containing 0.
Vet Rec
January 2025
Department of Animal and Agriculture, Hartpury University, Gloucester, UK.
Background: There is limited research on how rodent owners use and perceive veterinary services and what the demand for pet insurance for these species is.
Methods: An online survey of owners of pet rodents (guinea pigs, hamsters, rats, gerbils and mice) measured owner confidence in recognising signs of illness, their opinions on and use of veterinary services and their willingness to purchase pet insurance.
Results: A total of 1700 respondents completed the survey.
Int J Antimicrob Agents
January 2025
School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China. Electronic address:
The prevalence of herpes simplex virus type 1 (HSV-1) infection and the emergence of drug-resistant HSV-1 strains posts a significant global health challenge, necessitating the urgent development of effective anti-HSV-1 drugs. As one of the most prevalent molecular chaperones, heat shock protein 90 α (Hsp90α) has been extensively demonstrated to regulate a range of viral infections, thus representing a promising antiviral target. In this study, we identified JD-13 as a novel Hsp90α inhibitor and explored its capability in inhibiting HSV-1 infection.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA.
An understanding of intracellular mechanisms by which fentanyl and other synthetic opioids exert adverse effects on breathing is needed. Using freely moving adult male guinea pigs, we administered the nitric oxide synthase (NOS) inhibitor, L-NAME (N-nitro-L-arginine methyl ester), to determine whether nitrosyl factors, such as nitric oxide and S-nitrosothiols, play a role in fentanyl-induced respiratory depression. Ventilatory parameters were recorded by whole body plethysmography to determine the effects of fentanyl (75 μg/kg, IV) in guinea pigs that had received a prior injection of vehicle (saline), L-NAME or the inactive D-isomer, D-NAME (both at 50 μmol/kg, IV), 15 min beforehand.
View Article and Find Full Text PDFNutrients
January 2025
Section of Preclinical Disease Biology, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark.
Children and teenagers display a distinct metabolic dysfunction-associated steatohepatitis (MASH) phenotype, yet studies of childhood MASH are scarce and validated animal models lacking, limiting the development of treatments. Poor vitamin C (VitC) status may affect MASH progression and often co-occurs with high-fat diets and related metabolic imbalances. As a regulator of DNA methylation, poor VitC status may further contribute to MASH by regulating gene expression This study investigated guinea pigs-a species that, like humans, depends on vitC in the diet-as a model of pediatric MASH, examining the effects of poor VitC status on MASH hallmarks and global DNA methylation levels.
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