Date of Award

7-8-2024

Publication Type

Thesis

Degree Name

M.Sc.

Department

Biological Sciences

Keywords

Cerebral Blood Flow;Endothelium;Mechanosensation;Notch1;Shear Stress;Vascular Endothelial Growth Factor

Supervisor

A. Bain

Abstract

Notch1 has been recognized as an essential regulator of peripheral vascular endothelial function in response to vascular wall shear stress, perhaps partly through interactions with vascular endothelial growth factors (VEGFA); however, data on its activity and impact on cerebrovascular function are limited. Cerebral blood flow (CBF) and consequently shear rate (measured via simultaneous ultrasound of vertebral and internal carotid arteries) were manipulated in 14 (8M) young (27±4 yrs) healthy (BMI: 23±2 kg/m2) participants through 5min of hypercapnia (+9 PaCO2) and hypocapnia (-10 PaCO2) using dynamic end-tidal forcing. At baseline, hypercapnia, and hypocapnia, simultaneous blood samples were drawn from the radial artery and internal jugular bulb. All values are mean±SD. At baseline, the concentration of Notch1 was similar in the jugular vein (1054±1389 pg/mL) compared to the radial artery (840±962, P=0.255), and the average cerebral exchange (-158±392 ng/min) was statistically similar to zero (P=0.154). In hypercapnia, there was no significant change in Notch1 exchange (Notch1: -76±406 ng/min, P=1.026) from baseline. However, in hypocapnia the exchange of Notch1 flipped to an average uptake (105±353 ng/min, P=0.194), attributed to a significantly elevated arterial (+362±512 pg/mL, P=0.032) but not jugular venous (-42±496 pg/mL, P=1.00) concentration from baseline. Like Notch1, there was no change in VEGFA cerebral exchange across conditions. However, in hypercapnia, the concentration of VEGFA in the radial artery was significantly elevated (189±85 pg/mL, P=0.034) from baseline. There were no strong associations between Notch1 and VEGFA. Since hypercapnia and the resultant increase in cerebral shear rate had no impact on jugular venous Notch1 concentrations, shear-mediated Notch1 activity may be minimal in the brain. Accordingly, the increased radial concentration with hypocapnia is likely attributed to the known effects of hypocapnia to increase peripheral vascular shear stress.

Download

Included in

Physiology Commons

Share

COinS