Circadian variation of blood pressure and the vascular response to asynchronous stress.
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ABSTRACT:
SUBMITTER: Curtis AM
PROVIDER: S-EPMC1802007 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundLarge blood pressure (BP) variability may contribute to stroke and dementia, but the mechanisms are largely unknown.ObjectivesThis study investigated the association of BP variation, considering its magnitude and direction, with the presence and progression of subclinical brain disease in the general population.MethodsThis study included 2,348 participants age ≥55 years from a prospective cohort study. BP was measured at each visit every 3 to 4 years from 1990 onward. Brain magnetic resonance imaging (MRI) was performed at all visits from 2005 onward. The authors primarily assessed variation as the absolute difference in BP divided by the mean over 2 sequential visits for both systolic BP (SBP) and diastolic BP (DBP), and further assessed the direction of the variation. The authors investigated the multivariate-adjusted associations of BP variation with subsequent measurements of MRI markers of cerebral small vessel disease, brain tissue volumes, and white matter microstructural integrity. Longitudinal changes in these markers also were assessed.ResultsA large SBP variation (top vs. bottom tertiles), measured on average 7 years preceding brain MRI, was associated with higher odds of having severe white matter hyperintensities (WMH) (odds ratio [OR]: 1.32; 95% confidence interval [CI]: 1.21 to 1.43), lacunes (OR: 1.25; 95% CI: 1.04 to 1.48), and microbleeds (OR: 1.16; 95% CI: 1.03 to 1.31). Similarly, this variation was associated with smaller total brain volume and worse white matter microstructural integrity (all p < 0.001). A large SBP variation was also associated with the progression of WMH (rate ratio [RR]: 1.14; 95% CI: 1.02 to 1.27). Higher burdens of these brain imaging markers were observed with both large rises and falls in SBP. Similar findings were observed for DBP variation.ConclusionsElevated BP variation was associated with a wide range of subclinical brain structural changes, including MRI markers of cerebral small vessel disease, smaller brain tissue volumes, and worse white matter microstructural integrity. These subclinical brain changes could be the underlying mechanisms linking BP variation to dementia and stroke.
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Project description:As the central pacemaker, the suprachiasmatic nucleus (SCN) has long been considered the primary regulator of blood pressure circadian rhythm; however, this dogma has been challenged by the discovery that each of the clock genes present in the SCN is also expressed and functions in peripheral tissues. The involvement and contribution of these peripheral clock genes in the circadian rhythm of blood pressure remains uncertain. Here, we demonstrate that selective deletion of the circadian clock transcriptional activator aryl hydrocarbon receptor nuclear translocator-like (Bmal1) from smooth muscle, but not from cardiomyocytes, compromised blood pressure circadian rhythm and decreased blood pressure without affecting SCN-controlled locomotor activity in murine models. In mesenteric arteries, BMAL1 bound to the promoter of and activated the transcription of Rho-kinase 2 (Rock2), and Bmal1 deletion abolished the time-of-day variations in response to agonist-induced vasoconstriction, myosin phosphorylation, and ROCK2 activation. Together, these data indicate that peripheral inputs contribute to the daily control of vasoconstriction and blood pressure and suggest that clock gene expression outside of the SCN should be further evaluated to elucidate pathogenic mechanisms of diseases involving blood pressure circadian rhythm disruption.
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