Abstract
BackgroundAnimal models have become valuable experimental tools for understanding the pathophysiology and therapeutic interventions in cardiovascular disease. Yet to date, few studies document the age- and sex-related differences in arterial pressure, circadian rhythm, and renal function in normotensive mice under basal conditions, across the life span. We hypothesized that mice display similar sex- and age-related differences in arterial pressure and renal function to humans.MethodsMean arterial pressure (MAP) and circadian rhythm of arterial pressure were measured over 3 days via radiotelemetry, in 3- and 5-month-old (adult) and 14- and 18-month-old (aged) FVB/N and in 5-month-old (adult) C57BL/6 male and female normotensive mice. In FVB/N mice, albuminuria from 24-h urine samples as well as body, heart, and kidney weights were measured at each age.ResultsTwenty-four-hour MAP was greater in males than females at 3, 5, and 14 months of age. A similar sex difference in arterial pressure was observed in C57BL/6 mice at 5 months of age. In FVB/N mice, 24-h MAP increased with age, with females displaying a greater increase between 3 and 18 months of age than males, such that MAP was no longer different between the sexes at 18 months of age. A circadian pattern was observed in arterial pressure, heart rate, and locomotor activity, with values for each greater during the active (night/dark) than the inactive (day/light) period. The night-day dip in MAP was greater in males and increased with age in both sexes. Albuminuria was greater in males than females, increased with age in both sexes, and rose to a greater level in males than females at 18 months of age.ConclusionsArterial pressure and albuminuria increase in an age- and sex-specific manner in mice, similar to patterns observed in humans. Thus, mice represent a useful model for studying age and sex differences in the regulation of arterial pressure and renal disease. Understanding the mechanisms that underlie the pathophysiology of cardiovascular disease may lead to new and better-tailored therapies for men and women.
Highlights
Animal models have become valuable experimental tools for understanding the pathophysiology and therapeutic interventions in cardiovascular disease
Sex differences in 24-h arterial pressures, heart rate (HR), and locomotor activity across the lifespan Twenty-four-hour mean arterial pressure (MAP) was greater in males than females (F(1, 75) = 42.6, Psex < 0.0001), being ~5 mmHg (P < 0.05), ~7 mmHg (P < 0.005) and ~8 mmHg (P < 0.0001) greater in males than females at 3, 5, and 14 months of age, respectively (Fig. 1a)
Our study demonstrates that similar to humans, arterial pressure and albuminuria increase in a sex- and agespecific manner in mice, including different strains
Summary
Animal models have become valuable experimental tools for understanding the pathophysiology and therapeutic interventions in cardiovascular disease. Few studies document the age- and sex-related differences in arterial pressure, circadian rhythm, and renal function in normotensive mice under basal conditions, across the life span. We hypothesized that mice display similar sex- and age-related differences in arterial pressure and renal function to humans. It is well established that age- and sex-related differences exist in the regulation of arterial pressure. During their reproductive years, women have lower average systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) than age-matched men [1,2,3]. It is established that SAP and DAP are highest during the daytime and decrease by approximately 10–20% during the nighttime, with day-night differences in arterial pressure being similar in males and females [12, 14, 15]. It is imperative that strong similarities exist between humans and these animal models if knowledge translation is to be successful
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