Biology subjects

Loenstrup, M.

Publications and source records attributed to Loenstrup, M..

2 recordsLinked to original sources

bioRxiv2021

Impaired dynamics of brain precapillary sphincters and first order capillaries explains reduced neurovascular functions in aging

The microvascular inflow tract (MIT), comprising the penetrating arterioles, precapillary sphincters, and first order capillaries, is the bottleneck for brain blood flow and energy supply. However, the exact structural and functional alterations of the MIT during aging remain elusive. In vivo 4-dimensional two-photon imaging showed an age-dependent decrease in vaso-responsivity, with reduced sensitivity of the MIT to pinacidil and papaverine, vasoconstrictor endothelin-1, and nitric oxide synthase inhibitor L-NAME. This was accompanied by an age-dependent decrease in capillary density close to the arterioles and loss of pericyte processes, though the number of pericyte somas and pericyte SMA density were preserved. The age-related reduction in vascular reactivity was most pronounced at precapillary sphincters, highlighting their crucial role in capillary blood flow regulation. Mathematical modeling revealed dysregulated but preserved pressure and flow in aged mice during vasoconstriction. Preventing reduced responsivity of the MIT may ameliorate the blood flow decrease associated with aging-related brain frailty.

neuroscience↗

bioRxiv2020

Nitric oxide, KATP channels and endothelin-1 modulate brain pericyte function, vascular tone and neurovascular coupling

Neurotransmitter-mediated signaling correlates strongly to changes in cerebral blood flow (CBF), and functional neuroimaging relies on the robust coupling between activity and CBF, i.e. neurovascular coupling (NVC). We here reveal that key endothelial signaling molecules, nitric oxide (eNO) and endothelin-1 (ET1), modulate pericyte contractility and that pericyte ATP-sensitive potassium (KATP) channels interact with endothelial factors to modulate vascular tone and NVC. We show that NVC requires local synthesis of cGMP, but not NO derived from endothelial cells. The potent endothelial vasoconstrictor ET1 contracted pericytes by IP3 receptor mediated Ca2+ release and blocked NVC. In comparison, pericyte KATP channel openers increased the diameter of capillaries by deactivation of L-type Ca2+ channels while KATP blockers shortened the NVC response. All vasoactive stimuli produced the largest diameter changes at the first capillary that branches off from the penetrating arteriole. Our results reveal that three different signaling pathways mediate the effects of NO, ET1 and KATP channels on brain pericytes and capillary blood flow by mechanisms similar to vascular smooth muscle despite great differences in morphology.

neuroscience↗