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 (Y(HF)) 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 (A(HF)) compared with aged sham HF (A(SHAM)) rats, and in A(HF) compared with Y(HF) rats. Renal and splenic SND responses to hyperthermia (colonic temperature increased to 41.5°C) were determined in anesthetized Y(HF), young sham (Y(SHAM)), A(HF), and A(SHAM) Fischer rats. HF was induced by myocardial infarction and documented using echocardiographic, invasive, and postmortem measures. The severity of HF was similar in Y(HF) and A(HF) rats. SND responses to heating were attenuated in Y(HF) compared with Y(SHAM) rats, demonstrating an effect of HF on SND regulation in young rats. In contrast, A(HF) and A(SHAM) rats demonstrated similar SND responses to heating, suggesting a prominent influence of age on SND regulation in A(HF) rats. Splenic SND and MAP responses to heating were similar in Y(HF), A(HF), and A(SHAM) 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.

Fig. 1.

Echocardiographic data [fractional shortening (FS) (A), ratio of left atrial diameter (LA) and aortic root diameter (Ao) (LA/Ao) (B), left ventricular internal diameter in diastole (LVIDd) (C), and left ventricular internal diameter in systole (LVIDs) (D)] from young sham heart failure (Y_SHAM), young heart failure (Y_HF), aged sham heart failure (A_SHAM), and aged heart failure (A_HF) rats. P < 0.05 vs. age-matched sham groups (*) and vs. young condition-matched groups (†).

Fig. 2.

Invasive [left ventricular end-diastolic pressure (LVEDP) (A)] and morphometric [right ventricle weight-to-body weight ratio (RV/BW) (B) and lung weight-to-body weight ratio (LW/BW) (C)] data from Y_SHAM, Y_HF, A_SHAM, and A_HF rats. *P < 0.05 vs. age-matched sham groups (*) and vs. young condition-matched groups (†).

Fig. 3.

Changes in renal sympathetic nerve discharge (SND), splenic SND, mean arterial pressure (MAP), and heart rate (HR) during increases in internal body temperature (Tc) from 38 to 41.5°C in Y_SHAM (▴), Y_HF (▵), A_SHAM (●), and A_HF (○) rats. P < 0.05, Y_SHAM vs. control (38°C) values (*), A_HF, A_SHAM, and Y_HF vs. control (38°C) values (**), Y_SHAM vs. Y_HF and A_SHAM groups (†), and Y_HF vs. A_HF (‡).

Fig. 4.

Traces of integrated SND bursts (renal and splenic) and pulsatile arterial pressure (AP) recorded during control (38°C) and after increasing Tc to 41°C in Y_SHAM, Y_HF, A_SHAM, and A_HF rats. MAP values for each period are shown below the pulsatile AP traces. Horizontal calibration is 500 ms.