The emerging significance of circadian rhythmicity in microvascular resistance

ABSTRACT

The Earth’s rotation generates environmental oscillations (e.g., in light and temperature) that have imposed unique evolutionary pressures over millions of years. Consequently, the circadian clock, a ubiquitously expressed molecular system that aligns cellular function to these environmental cues, has become an integral component of our physiology. The resulting functional rhythms optimize and economize physiological performance: perturbing these rhythms, therefore, is frequently deleterious. This perspective article focuses on circadian rhythms in resistance artery myogenic reactivity, a key mechanism governing tissue perfusion, total peripheral resistance and systemic blood pressure. Emerging evidence suggests that myogenic reactivity rhythms are locally generated in a microvascular bed-specific manner at the level of smooth muscle cells. This implies that there is a distinct interface between the molecular clock and the signalling pathways underlying myogenic reactivity in the microvascular beds of different organs. By understanding the precise nature of these molecular links, it may become possible to therapeutically manipulate microvascular tone in an organ-specific manner. This raises the prospect that interventions for vascular pathologies that are challenging to treat, such as hypertension and brain malperfusion, can be significantly improved.

KEYWORDS:

• Vascular smooth muscle cells
• systemic hemodynamics
• total peripheral resistance
• cystic fibrosis transmembrane conductance regulator
• CFTR
• tumor necrosis factor
• TNF
• cerebral arteries

Acknowledgements

The authors thank Alexandra Erin Papaelias for graphic design and preparation of the figures. We thank Danny D Dinh and Chloe Ng for assistance with data collection.

Data availability statement

The data that support the findings of this study are available within the article and its supplementary information file. All data can be made available by the corresponding author upon request.

Disclosure statement

DL and JTK are consultants for Qanatpharma AG (Stans, Switzerland). SSB is executive board member of Qanatpharma AG and Aphaia Pharma AG (Zug, Switzerland). Neither Qanatpharma AG nor Aphaia Pharma AG had any financial or intellectual involvement in this article.

Author contribution

JTK and SSB wrote the first draft of this article. All authors contributed equally to the conceptualization, literature research and revision of the final manuscript.

Supplemental Material

Supplemental data for this article can be accessed on the publisher’s website

Additional information

Funding

Funding for publication charges was provided by The Brain Aneurysm Foundation (Thomas J. Tinlin Chair of Research Award) and a Ted Rogers Centre for Heart Research (University of Toronto) research grant. SSB receives stipend support from a Heart and Stroke Foundation of Ontario Mid-Career Investigator award.