The thyrotropin‐releasing hormone analog Taltirelin augments the hypercapnic ventilatory response in CO2‐insensitive Brown Norway but not Sprague Dawley rats (1092.6)

Abstract

Thyrotropin‐releasing hormone (TRH) is an excitatory neuropeptide that may modulate the hypercapnic ventilatory response (HCVR). We have found reduced expression of TRH in the medullary raphe in Brown Norway (BN) compared to Sprague Dawley (SD) rats. Herein we tested the hypothesis that the reduced TRH in the BN rat contributes to their blunted HCVR by measuring ventilation (VE), arterial blood gases, and rectal temperature (TR) in BN and SD rats during exposures to room air (RA) or hypercapnia (7% CO2) before and 1 hr after IP injections of saline, or 0.3 mg/kg or 1.0 mg/kg of the TRH analog Taltirelin (TAL). VE in RA did not differ among strains during all control studies, but VE increased after low and high dose TAL in both strains (p蠄0.05), with a greater increase in BN rats (p<0.05). The slope of the relationship between VE and PaCO2 breathing RA and 7% CO2 (ΔVE/ΔPaCO2) was lower in BN (0.4 ± 0.3) vs. SD (10.2 ± 1.5) rats after saline (p<0.05), and increased in BN (6.3 ± 1.0; p<0.05) but not SD (8.2 ± 1.2; p=0.15) rats after high dose TAL, where ΔVE/ΔPaCO2 no longer differed among the strains (p=0.207). TR also significantly increased in BN rats after high dose TAL (+1.1 ± 0.1°C; p<0.001), but was unaffected in SD rats (+0.1 ± 0.2°C; p=0.523). These data suggest an increased sensitivity to TRH receptor stimulation in BN rats, consistent with the concept that reduced endogenous TRH expression contributes to their blunted HCVR.Grant Funding Source: Supported by NIH HL097033