Effects of a Chronic Mental Stress Intervention Protocol on Vasomotor Function in Common Carotid Artery from Wistar-Kyoto and Spontaneously- Hypertensive Rats

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.