| dc.description.abstract | ABSTRACT
Chronic mental stress is emerging as a cardiovascular disease (CVD) risk factor;
however, the underlying physiological mechanisms to explain how chronic mental stress may be
causing CVD are still under investigation. Previous literature has demonstrated that chronic
mental stress can induce endothelial dysfunction, which is a well-known independent risk factor
for CVD. The purpose of this study was to further investigate the underlying pathophysiological
mechanisms that may be contributing to this endothelial dysfunction, in the normotensive
Wistar-Kyoto (WKY) and Spontaneously Hypertensive (SHR) rat models. A chronic mental
stress protocol, known as the Unpredictable Chronic Mild Stress (UCMS) protocol, was used to
induce chronic mental stress in the animals in order to determine its effects on endothelial
function. Animals were divided up into four groups: WKY CON, WKY UCMS, SHR CON, and
SHR UCMS. To test the efficacy of the UCMS protocol, behavioural tests were performed to
confirm the presence of mental stress in the animals in the UCMS groups compared to the
control groups (Coat status: WKY: p<0.0001, SHR: p<0.0006; Splash test (Grooming
Frequency): WKY: p=0.5581, SHR: p=0.0050). Unexpectedly, compared to WKY CON
endothelium-dependent, acetylcholine (ACh)-stimulated vasocontraction (Maximum Amp
(MAX): 27.25±5.95, Area Under the Curve (AUC): 54.22±10.98, EC50: 2.58±0.79), UCMS was
found to significantly attenuate endothelium-dependent, ACh-stimulated MAX (11.86±2.91;
p=0.043) and AUC (24.87±5.43; p=0.037), but not EC50 (2.48±1.20; p=0.913). Likewise,
compared to SHR CON endothelium-dependent, ACh-stimulated vasocontraction (MAX:
48.5±9.0, AUC: 84.3±15.4, EC50: 2.44±0.70), UCMS was found to attenuate endotheliumdependent,
ACh-stimulated MAX (33.40±6.51; p=0.083), AUC (65.42±12.76; p=0.170), and
EC50 (1.62±0.43; p=0.202), however this attenuation did not reach significance. Furthermore,
compared to WKY CON endothelium-dependent, ACh-stimulated vasorelaxation MAX:
92.43±3.08, AUC: 300.6±17.84, EC50: 95.25±32.16), UCMS was found to significantly augment
endothelium-dependent, ACh-stimulated AUC (349.9±13.42; p=0.040), and insignificantly
augment endothelium-dependent, ACh-stimulated MAX (101.0±1.35; p=0.241) and EC50
(41.0±8.44; p=0.120). Likewise, compared to SHR CON endothelium-dependent, AChstimulated
vasorelaxation (MAX: 83.81±3.19, AUC: 282.4±12.19, EC50: 69.41±25.53), UCMS
was found to augment endothelium-dependent, ACh-stimulated MAX (88.65±2.63; p=0.250),
AUC (287.0±11.09; p=0.781), and EC50 (87.83±32.3; p=0.669), however this augmentation did
not reach significance. Dose-dependent response curves to sodium nitroprusside (SNP) and
U46619 were similar across all groups, suggesting that the attenuated vasocontraction and
enhanced vasorelaxation was not due to UCMS having an effect on vascular smooth muscle
(VSM) sensitivity, but is more likely due to a reduction in endothelium-derived contracting
factor (EDCF) production/bioavailability and/or an increase in endothelium-derived relaxing
factor (EDRF) production/bioavailability. | en |
