Autonomic Dysfunction Determines Stress‐Induced Cardiovascular and Immune Complications in Mice

Abstract

BackgroundClinical studies suggest that acute inflammation in patients with elevated heart rate (HR) increases morbidity and mortality. The SJL/J (SJL) inbred mouse strain is a unique genetic model that has higher HR and systemic and vascular inflammation compared with C3HeB/FeJ (C3HeB) mice. The goal of this study was to investigate the role of stress on cardiac and vascular complications between 2 strains.Methods and ResultsRadiotelemetry was used for continuous recordings of HR and blood pressure in mice. Hemodynamic differences between mouse strains were very small without stress; however, tail-cuff training generated mild stress and significantly increased HR (≈2-fold) in SJL compared with C3HeB mice. Circulating proinflammatory monocytes (CD11b+Ly6CHi) significantly increased in SJL mice but not in C3HeB mice after stress. Presence of Ly6C+ cells in injured carotids was elevated only in SJL mice after stress; however, a transfer of bone marrow cells from SJL/C3HeB to C3HeB/SJL chimeras had no effect on HR or vascular inflammation following stress. Arterial inflammation (VCAM-1+) was greater in SJL inbred mice or SJL recipient chimeras, even without stress or injury. HR variability was reduced in SJL mice compared with C3HeB mice.ConclusionsWe found that impaired parasympathetic activity is central for stress-induced elevation of HR and systemic and vascular inflammation; however, immune cells from stress-susceptible mice had no effect on HR or vascular inflammation in stress-protected mice.

Tail‐Cuff Technique and Its Influence on Central Blood Pressure in the Mouse

“…Moreover, it is standard to train mice so that they become accustomed to the investigator and total process; however, our results are similar to those obtained by others23, 24 in that no reduction in blood pressure or heart rate was seen as a result of repeated exposure to the technique. On the contrary, repeated restraint and tail‐cuff recording over 5 consecutive days has been used by others as a method to induce stress,23 in support of the concept that the restraint component of the assay is associated with hemodynamic stress. However, it is our observation that mice become familiar with both the handling and the process of tail‐cuff, which can facilitate the collection of data.…”

“…It is believed that the mice habituate to the tail‐cuff procedure following repeated exposure and there is a common practice to “train” mice before starting an experiment 10, 21, 22. However, there is evidence that this does not happen 23, 24. Moreover, the tail‐cuff technique has been used to model stress that was defined by measuring heart rate 23…”

“…10,21,22 However, there is evidence that this does not happen. 23,24 Moreover, the tail-cuff technique has been used to model stress that was defined by measuring heart rate. 23 A further important consideration is the anatomical position from which the measurements are taken.…”

“…23,24 Moreover, the tail-cuff technique has been used to model stress that was defined by measuring heart rate. 23 A further important consideration is the anatomical position from which the measurements are taken. Telemetry devices take measurements directly from inside a major blood vessel, commonly the aortic arch or abdominal aorta in the mouse.…”

Role of Axl in T-Lymphocyte Survival in Salt-Dependent Hypertension

“…However, many laboratories including ours have validated tail-cuff BP measurements by radiotelemetry method. Our recent study in inbred mouse strains showed significant correlation between our tail-cuff training protocol and radiotelemetry measurements of systolic BP 39 . We are confident in our results collected by tail-cuff method because of BP levels reflected degree of arterial remodeling obtained by histology across mice after DOCA-salt.…”