First Author | Methner C | Year | 2019 |
Journal | Am J Physiol Heart Circ Physiol | Volume | 317 |
Issue | 2 | Pages | H255-H263 |
PubMed ID | 31125259 | Mgi Jnum | J:278398 |
Mgi Id | MGI:6323723 | Doi | 10.1152/ajpheart.00097.2019 |
Citation | Methner C, et al. (2019) Pericyte constriction underlies capillary derecruitment during hyperemia in the setting of arterial stenosis. Am J Physiol Heart Circ Physiol 317(2):H255-H263 |
abstractText | 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. |