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Abstract-The objective of this study was to determine the effect of chronic stress exposure on the circadian pattern of cardiovascular responses in mice. Using male C57BL6 mice with carotid arterial catheters, we tested the effect of 7 days of intermittent shaker stress on body weight, food intake, drinking activity, plasma corticosterone, mean arterial pressure (MAP), and heart rate. The stress was delivered automatically for 2-minute periods (150 cycles/min), 45 times/d for 7 days. Plasma corticosterone was significantly increased in acutely and chronically stressed mice, with a partial attenuation in the chronic condition. Stress increased water intake, produced no change in food intake, and significantly decreased body weight (5% change). MAP and heart rate were measured continuously on stress days 1, 3, and 7 and during the basal and recovery periods. Chronic stress did not produce a sustained increase in MAP; however, there was an increase in MAP during the first stress day and a decrease during the recovery period. There was a circadian pattern in the pressor responses, with greater increases seen during the light period (nonactive phase) than in the dark period (ϩ24% versus ϩ11% on stress day 3, light versus dark). The results suggest that a stress delivered during the nonactive phase represents a higher cardiovascular risk. Key Words: blood pressure Ⅲ heart rate Ⅲ corticosterone Ⅲ circadian rhythm L ifestyle stress is a risk factor for human diseases, including cancer, stroke, psychological disorders, and heart disease. There is a circadian pattern in the incidence of cardiovascular pathologies, with a higher frequency of heart attacks, strokes, and arrhythmias during the morning hours. [1][2][3] Stressful conditions may also be a precipitating factor in the occurrence of cardiovascular accidents.In animals, stress exposure produced by a variety of methods provokes a cascade of autonomic adjustments characterized by increased blood pressure (BP), increased heart rate (HR), and behavioral alterations. Most studies of stress biology have been conducted in rats, providing information on changes in cardiovascular function and eating and drinking behaviors. 4 -10 However, one complication of the experimental paradigms is that the stress effects can be enhanced by animal handling, noise, or pain, as seen in the forced swim test, air jet exposure, and physical restraint. 4,8,11 Shaker stress is a mild, pain-free stimulus that elicits reproducible changes in BP, HR, sympathetic activity, and stress hormone secretion. 12,13 There is no information on the application of shaker stress in mice and no data on the long-term effects of shaker stress on the cardiovascular system or on drinking and eating patterns.For investigations in mice, we developed a computerized system for chronic, continuous BP recording and combined this with electronic recording of licking activity for analysis of circadian patterns. 14,15 This methodology was applied to the investigation of the effects of stress on BP and HR responses and dri...

We used oxytocin knockout (OTKO) mice to investigate the role of oxytocin in regulation of blood pressure, heart rate and stress reactivity (pressure reactivity and plasma corticosterone). Male OTKO and control wild-type mice with carotid arterial catheters were exposed to intermittent shaker stress for 7 days (2 min stressors, 45 times per day). Mean arterial pressure (MAP) and heart rate (HR) were recorded continuously (24 h) before stress (basal), on stress days 1, 3 and 7 (S1, S3 and S7) and 1 day poststress (recovery). Plasma corticosterone (Cort) was measured before stress and 30 min after the last stress on day 7. Twenty-four hour averages of MAP and HR were lower in OTKO mice than in controls (P < 0.0001 and P < 0.005, respectively) with a significant diurnal rhythm. Chronic stress (S1 and S3) produced an increase in 24 h average MAP in OTKO mice, but not in controls. There were no stress-related changes in 24 h average HR values between control and OTKO mice. The immediate pressor responses were analysed during the dark and light periods (19.00 and 08.00 h). During the dark period, stress-induced pressor responses were observed only in OTKO mice (S1 and S3). In the light period, stress-induced MAP increases were seen on all days in OTKO mice and on days S1 and S3 in controls. There were no differences in baseline Cort between the groups; however, OTKO mice showed a reduced response to chronic stress (+298 versus +411%, OTKO mice versus controls, P < 0.005). In conclusion, oxytocin deficiency alters the endocrine and pressor responses to chronic stress, suggesting that the endogenous oxytocin system is important in regulating the stress-induced pressor response.

Measuring the overall nocturnal serum melatonin profile during darkness may help to differentiate children and adolescents with major depression without psychosis from those with psychosis and from controls.

Aim To determine whether pharmacological blockade of angiotensin (Ang) ATI receptors alters the cardiovascular, metabolic, and angiotensin-converting enzyme (ACE and ACE2) responses to a fructose diet in mice. Methods C57BL male mice were fed with a 60% fructose diet for 8 weeks in combination with losartan treatment on week 9 (30 mg/kg per day). Blood pressure (BP), heart rate (HR), and autonomic balance were monitored using radiotelemetry with spectral analysis. Renal ACE and ACE2 activity and protein levels as well as Ang II and Ang 1-7 were measured. Results Fructose impaired glucose tolerance and increased plasma cholesterol and insulin. These effects were not corrected by losartan treatment. Fructose increased BP and HR but only during the dark period. Short-term losartan treatment decreased BP by 16% in the fructose group but had no effect in controls. This was accompanied by a decrease in BP variance and its low-frequency component. Fructose increased Ang II (plasma and kidney) and ACE 2 (renal activity and protein expression). Losartan alone increased plasma Ang II in plasma and ACE2 in kidney. There were no changes in renal Ang 1-7 levels. Conclusions Losartan reversed the pressor effect of a high fructose diet, demonstrating that there are prominent interactions between a dietary regimen that produces glucose intolerance and an antihypertensive drug that antagonizes Ang signaling. The mechanism of change may be via renal Ang II rather than the ACE2/Ang 1-7 pathway because the fructose losartan combination resulted in lowered renal Ang II without changes in Ang 1-7.