SEX DIFFERENCES IN RESPONSE TO STRESS IN MALE AND FEMALE HYPERTENSIVE SCHLAGER MICE

Abstract

Objective: The inbred hypertensive mouse strain (BPH/2) and a normotensive strain (BPN/3) are thought to be a neurogenic form of hypertension. The aim of the current study was to compare the cardiovascular characteristics of male and female hypertensive and normotensive mice to determine any sex differences in the underlying mechanisms. Design and method: 12-week-old hypertensive BPH/2J and normotensive BPN/3J male and female mice were implanted with telemetry probes to record blood pressure (BP), heart rate and activity. Cardiovascular responses to restraint, dirty cage swap, feeding, enalaprilat and pentolinium were measured in conscious mice. Results: Mean, systolic, diastolic BP, heart rate and activity were similar in males and females but higher in BPH/2 than BPN/3 (n = 5–7). Day night differences in BP were 3 times higher in BPH/2 compared to BPN/3 (17 vs 6 mmHg respectively) but similar in male and female mice. The depressor responses to enalaprilat reduced BP by -11 ± 1 mmHg and was similar in both male strains but greater in female BPH/2 mice (-17 ± 1 mmHg). Blocking the sympathetic nervous system activity produced a 5-fold greater reduction in BP in male and female BPH/2 mice. The pressor response to restraint stress was higher in BPH/2 than BPN/3 but similar in the males and females of each strain. While the pressor response to dirty cage swap was greater in BPH/2 than BPN/3 mice, it was also greater in males than females. Treatment with a synthetic neurosteroid ganaxolone (5 mg/kg/day) for 2 weeks attenuated the pressor response to cage swap only in male BPH/2 mice and not in females. The percentage of time spent in a dark area compared to the light (indicating anxiety) was similar in males and females of both strains. Conclusions: While hypertension is similar in male and female BPH/2 mice the differential response to behavioral stress tests and their susceptibility of attenuation by ganaxolone in males and females suggests important differences in the central pathways controlling the adverse response to stress. Understanding these differences may be relevant to the higher cardiovascular risk observed in males.