In dystrophic hamsters losartan affects control of ventilation and dopamine D1 receptor density.
The BIO 14.6 hamster (DV), an animal model of limb-girdle muscular dystrophy, has elevated angiotensin AT1 receptors that may affect ventilation. Moreover, AT1 receptors may modulate expression of dopamine D1 receptors. We investigated if chronic treatment of BIO 14.6 hamsters (DL) with losartan, an AT1 receptor blocker, affects D1 receptor density in the striatum and nucleus tractus solitarius (NTS) and normalizes ventilation during exposure to air, hypoxia, following hypoxia, and hypercapnia, Ventilation was evaluated using plethysmography. Compared to the golden Syrian hamsters (GS), DV hamsters exhibited lower hypercapnic and hypoxic responsiveness and ventilation during hypercapnic exposure. Relative to GS, DL hamsters increased breathing frequency in air and maintained ventilation during hypercapnia. Post-hypoxic minute ventilation decline occurred in DV but not in DL or GS hamsters. DL hamsters exhibited higher D1 receptor density in the striatum and NTS relative to DV hamsters. Thus, in dystrophic hamsters chronic losartan treatment stimulated frequency of breathing and increased the density of D1 receptors.
Schlenker
Evelyn H
EH
Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, 414 East Clark St., Vermillion, SD 5760, United States. Evelyn.Schlenker@usd.edu
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006935:Hypercapnia / Q000188:drug therapy / Q000503:physiopathology; D000860:Hypoxia / Q000188:drug therapy / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008647:Mesocricetus; D049288:Muscular Dystrophies, Limb-Girdle / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects; D010991:Plethysmography / Q000379:methods; D012123:Pulmonary Ventilation / Q000187:drug effects*; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism*; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology; D018709:Statistics, Nonparametric; D013997:Time Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D017447:Receptors, Dopamine D1; D019808:Losartan