Background: Excitation-contraction coupling of the normotensive rat heart exhibits a time-of-day variation in its response to isoproterenol (ISO), with a decrease during the animal's active period. Pressure-induced hypertrophy is known to adversely affect the circadian clock in the heart and this study sets out to determine whether this alters the time-of-day variation in E-C coupling.
Method and results: Hearts from juvenile (6-8 week) and adult (24-28 week) spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were isolated during the animals active and resting periods. Left ventricular developed pressure (LVDP) recorded from isolated perfused adult SHR hearts did not show the night-time dip in response to ISO that was present in normotensive hearts. Left ventricular myocytes isolated from juvenile WKY and SHRs during the resting period had a higher systolic [Ca]i and faster rate of decay of the Ca- transient, under basal conditions and in response to 10 nmol/l ISO, than the active period. LV-myocytes isolated from adult WKYs had a similar time-of-day variation in their Ca-transient. However, LV-myocytes from adult SHRs had lost this diurnal variation in both basal systolic [Ca]i and in response to ISO. Adult SHR hearts were hypertrophic in comparison to age-matched WKYs, had disrupted cycling of the circadian genes CLOCK and Per2, and this was matched by depressed nNOS cycling.
Conclusion: The dip in response of the heart to ISO stimulation during the animal's active period is absent in adult SHRs. This may result from disruption to the circadian clock mechanism, which depresses the cycling of nNOS expression.