Effects of combined aging and heart failure on visceral sympathetic nerve and cardiovascular responses to progressive hyperthermia in F344 rats

Abstract

Sympathetic nerve discharge (SND) responses to hyperthermia are attenuated in aged rats without heart failure (HF) and in young HF (YHF) rats, demonstrating that individually aging and HF alter SND regulation. However, the combined effects of aging and HF on SND regulation to heat stress are unknown, despite the high prevalence of HF in aged individuals. We hypothesized that SND responses to heating would be additive when aging and HF are combined, demonstrated by marked reductions in SND and mean arterial pressure (MAP) responses to heating in aged HF (AHF) compared with aged sham HF (ASHAM) rats, and in AHF compared with YHF rats. Renal and splenic SND responses to hyperthermia (colonic temperature increased to 41.5°C) were determined in anesthetized YHF, young sham (YSHAM), AHF, and ASHAM Fischer rats. HF was induced by myocardial infarction and documented using echocardiographic, invasive, and postmortem measures. The severity of HF was similar in YHF and AHF rats. SND responses to heating were attenuated in YHF compared with YSHAM rats, demonstrating an effect of HF on SND regulation in young rats. In contrast, AHF and ASHAM rats demonstrated similar SND responses to heating, suggesting a prominent influence of age on SND regulation in AHF rats. Splenic SND and MAP responses to heating were similar in YHF, AHF, and ASHAM rats, indicating that the imposition of HF in young rats changes the regulatory status of these variables to one consistent with aged rats. These data suggest that the effect of HF on SND regulation to hyperthermia is age dependent.