The sex-related differences on cardiac electrical dysfunctionalities induced by in vivo angiotensin II treatment in male and female mice

Cardiovascular disease is a leading cause of death regardless of sex, however the influence of sex differences on cardiovascular disease requires more attention. Women frequently experience different symptoms than men which can lead to misdiagnosis or delayed treatment. In this study, the importance of sex has been evaluated in terms of electrical activity of the heart under the stimulation of chronic angiotensin II infusion.

In this study, the possible role and effect of sex-related differences on cardiac rhytm disturbances in response to chronic angiotensin II treatment was investigated.

8-11 week-old female (n=10) and male (n=10) C57BL/6 mice were purchased from a University Department. All animal procedures were approved by our Institutional Ethical Committee. Male and female mice were divided in four groups: control (sham-operated) male (n=5), angiotensin II-treated male (n=5), control (sham-operated) female (n=5), angiotensin II-treated female (n=5). Chronic angiotensin II treatment was conducted at the dose of 1.44 mg/kg/day for 14 days via subcutaneous osmotic mini-pump. Controls were treated in parallel with saline solution. Before the implantation of the pump (Day 0) and at the end of the 14-day-treatment period (Day 14), electrocardiogram (ECG) measurements were performed in all groups at the same conditions under isoflurane anesthesia. Statistical analysis was performed using one-way ANOVA and Tukey's as post-hoc test.

14-day angiotensin II infusion induced a significant reduction in heart rate compared to control group of each sexes. QT intervals which were prolonged compared to control at Day 14 also showed a failing condition of the heart. The duration of PR intervals were detected as significantly reduced in male angiotensin II-treated mice compared to the Day 14 recordings. This parameter is preserved in female mice treated with angiotensin II for 14 days.

Our study revealed that sex-related factors can play a possible role in the cardiac conduction activity stimulated by chronic angiotensin II treatment.