Hypertension and Disrupted Blood Pressure Circadian Rhythm in Type 2 Diabetic db/db Mice

Human Type 2 diabetes is associated with increased incidence of hypertension and disrupted blood pressure (BP) circadian rhythm. Db/db mice have been used extensively as a model of type 2 diabetes but their BP is not well characterized. In this study we used radiotelemetry to define BP and their circadian rhythm in db/db mice. We found that the systolic, diastolic, and mean arterial pressures were each significantly increased by 11, 8 and 9 mmHg in db/db mice compared to controls. In contrast, no difference was observed in pulse pressure or heart rate. Interestingly, both the length of time db/db mice were active (locomotor), and the intensity of locomotor activity were significantly decreased in db/db mice. In contrast to controls, the 12 hour light period average BP in db/db mice did not dip significantly from the 12 hour dark period. A partial Fourier analysis of the continuous 72 hour BP data revealed that the power and the amplitude of the 24 hour period length rhythm were significantly decreased in db/db mice compared to the controls. The acrophase was centered at 1:41 in control mice but became scattered from 18:05 to 2:36 in db/db mice. In addition to BP, the circadian rhythms of heart rate, and locomotor activity were also disrupted in db/db mice. The mean arterial pressure during the light period correlates with plasma glucose, insulin and body weight. Moreover, the oscillations of the clock genes DBP and Bmal1 but not Per1 were significantly suppressed in db/db mouse aorta compared to controls. In summary, our data shows that db/db mice are hypertensive with a disrupted BP, heart rate and locomotor circadian rhythm. Such changes are associated with suppressed oscillations of clock genes DBP and Bmal1 in vasculature. 10.1152/ajpheart.00257.2008