J Appl Physiol (1985). 2023 May 18. doi: 10.1152/japplphysiol.00688.2022. Online ahead of print.

ABSTRACT

90 million Americans suffer metabolic syndrome (MetSyn), increasing risk of diabetes and poor brain outcomes including neuropathology linked to lower cerebral blood flow (CBF)-predominantly in anterior regions. We tested the hypothesis total and regional CBF is lower in MetSyn more so in the anterior brain and explored three potential mechanisms. 34 Controls (25±5 yrs) and 19 MetSyn (30±9 yrs), with no history of cardiovascular disease/medications, underwent 4D flow magnetic resonance imaging (MRI) to quantify macrovascular CBF, while arterial spin labeling (ASL) quantified brain perfusion in a subset (n=38/53). Contributions of cyclooxygenase (COX; n=14), nitric oxide synthase (NOS, n=17), or endothelin receptor A signaling (ET_A; n=13) were tested with indomethacin, L-NMMA, and Ambrisentan, respectively. Total CBF was 20±16% lower in MetSyn (725±116 vs. 582±119 mL/min, P<0.001). Anterior and posterior brain regions were 17±18% and 30±24% lower in MetSyn; reductions were not different between regions (P=0.112). Global perfusion was 16±14% lower in MetSyn (44±7 vs. 36±5 mL/100g/min, P=0.002) and regionally in frontal, occipital, parietal, and temporal lobes (range 15-22%). The decrease in CBF with L-NMMA (P=0.004) was not different between groups (P=0.244), and Ambrisentan had no effect on either group (P=0.165). Interestingly, indomethacin reduced CBF more in Controls in the anterior brain (P=0.041), but CBF decrease in posterior was not different between groups (P=0.151). These data indicate adults with MetSyn exhibit substantially reduced brain perfusion without regional differences. Moreover, this reduction is not due to loss of NOS or gain of ET-1 signaling but rather a loss of COX vasodilation.

PMID:37199780 | DOI:10.1152/japplphysiol.00688.2022