Losartan affects Tyrosine Hydroxylase Protein Expression in the A2 Area and Hypoglossal Nucleus of Normal and Dystrophic Hamsters

Abstract

Angiotensin AT1 receptors affect production of tyrosine hydroxylase (TH), the rate‐limiting enzyme for production of catecholamines. AT1 receptors are colocalized with TH in the A2 region of the nucleus tractus solitaries and hypoglossal nucleus. We hypothesized that blocking AT1 receptors with losartan (L), an AT1 receptor antagonist, would decrease TH expression in the A2 and hypoglossal nucleus in normal (N) and dystrophic (D) hamsters. Two month old male N and D hamsters received tap water or L in drinking water at a dose of 50 mg/kg/day for 2.5 months. At 4.5 months, animals were sacrificed, brains perfused, cryoprotected, and frozen at ‐70° C. Brains were sliced at 35‐40 micrometers. Immunohistochemistry was performed using a mouse monoclonal TH primary antibody (1:10,000) visualized with DAB. ImageJ was used to evaluate A2 and hypoglossal areas and number of TH positive neurons. Losartan had no effect on hypoglossal areas, but decreased the number and density of TH positive neurons and in D hamsters, but not in N hamsters. In N and D hamsters TH positive neurons were predominately located in ventral regions of the hypoglossal nuclei. Losartan treatment eliminated this localization in both groups. In the A2 region no significant differences were observed in areas or number of positive TH neurons, but in D hamsters L decreased TH positive neuron density.Funded by: APS Undergraduate Summer Fellowship & P20 RR‐015567