Enhanced light-dark modulation of cardiovascular function in SPAK knock-in mice

Area of Science:

• Physiology
• Cardiovascular Biology
• Chronobiology

Background:

• Light-dark cycles and behavior regulate cardiovascular function daily.
• The STE20/SPS1-related proline-alanine-rich kinase (SPAK) kinase is crucial for ion transport and blood pressure regulation.
• The role of SPAK in day-night cardiovascular variation is not well understood.

Purpose of the Study:

• To investigate the association between SPAK genotype and day-night cardiovascular variation under a controlled light-dark schedule.
• To assess the influence of light-dark phase and activity state on cardiovascular parameters in SPAK knock-in (KI) and wild-type (WT) mice.

Main Methods:

• Radiotelemetry was used to record heart rate, systolic, diastolic, mean arterial, and pulse pressure in mice over three consecutive day-night cycles.
• Mice included SPAK knock-in (KI) and wild-type (WT) genotypes.
• Repeated-measures ANOVA was employed to analyze cardiovascular data, considering animal as the unit of analysis.

Main Results:

• WT mice showed no significant light-dark variation in most cardiovascular parameters, though effect sizes were notable.
• KI mice exhibited significant light-dark variation across cardiovascular parameters (p < 0.05).
• Activity state strongly influenced heart rate and blood pressure in both genotypes, while pulse pressure was less consistently affected.

Conclusions:

• The SPAK knock-in genotype is linked to heightened day-night modulation of cardiovascular function under a 12:12h light-dark protocol.
• Activity state remains a primary determinant of cardiovascular variability.
• Findings are preliminary due to exploratory nature and small sample size, warranting further investigation.