Pericyte constriction underlies capillary derecruitment during hyperemia in the setting of arterial stenosis.

Journal Article (Journal Article)

Capillary derecruitment distal to a coronary stenosis is implicated as the mechanism of reversible perfusion defect and potential myocardial ischemia during coronary hyperemia; however, the underlying mechanisms are not defined. We tested whether pericyte constriction underlies capillary derecruitment during hyperemia under conditions of stenosis. In vivo two-photon microscopy (2PM) and optical microangiography (OMAG) were used to measure hyperemia-induced changes in capillary diameter and perfusion in wild-type and pericyte-depleted mice with femoral artery stenosis. OMAG demonstrated that hyperemic challenge under stenosis produced capillary derecruitment associated with decreased RBC flux. 2PM demonstrated that hyperemia under control conditions induces 26 ± 5% of capillaries to dilate and 19 ± 3% to constrict. After stenosis, the proportion of capillaries dilating to hyperemia decreased to 14 ± 4% (P = 0.05), whereas proportion of constricting capillaries increased to 32 ± 4% (P = 0.05). Hyperemia-induced changes in capillary diameter occurred preferentially in capillary segments invested with pericytes. In a transgenic mouse model featuring partial pericyte depletion, only 14 ± 3% of capillaries constricted to hyperemic challenge after stenosis, a significant reduction from 33 ± 4% in wild-type littermate controls (P = 0.04). These results provide for the first time direct visualization of hyperemia-induced capillary derecruitment distal to arterial stenosis and demonstrate that pericyte constriction underlies this phenomenon in vivo. These results could have important therapeutic implications in the treatment of exercise-induced ischemia. NEW & NOTEWORTHY In the setting of coronary arterial stenosis, hyperemia produces a reversible perfusion defect resulting from capillary derecruitment that is believed to underlie cardiac ischemia under hyperemic conditions. We use optical microangiography and in vivo two-photon microscopy to visualize capillary derecruitment distal to a femoral arterial stenosis with cellular resolution. We demonstrate that capillary constriction in response to hyperemia in the setting of stenosis is dependent on pericytes, contractile mural cells investing the microcirculation.

Full Text

Duke Authors

Cited Authors

  • Methner, C; Mishra, A; Golgotiu, K; Li, Y; Wei, W; Yanez, ND; Zlokovic, B; Wang, RK; Alkayed, NJ; Kaul, S; Iliff, JJ

Published Date

  • August 1, 2019

Published In

Volume / Issue

  • 317 / 2

Start / End Page

  • H255 - H263

PubMed ID

  • 31125259

Pubmed Central ID

  • PMC6732474

Electronic International Standard Serial Number (EISSN)

  • 1522-1539

Digital Object Identifier (DOI)

  • 10.1152/ajpheart.00097.2019

Language

  • eng

Conference Location

  • United States