Purinergic Receptor Activation Protects Glomerular Microvasculature from Increased Mechanical Stress in Angiotensin II-Induced Hypertension: A Modeling Study
Year: 2025
Type: article
Abstract: Angiotensin II (Ang II)-induced hypertension increases afferent (AA) and efferent (EA) arteriole resistances via the actions of Ang II on the AT1 receptor. In addition to the increased interstitial levels of Ang II, the increased arterial pressure increases interstitial ATP concentrations. In turn, ATP acts on the purinergic receptors P2X1 and P2X7 to constrict the AA, preventing increases in plasma flow and single-nephron GFR (SNGFR). While the hemodynamic effects of P2 activation have been characterized, the resulting increases in mechanical stresses (shear stress and circumferential hoop stress) on the glomerular microvasculature have not been quantified. A mathematical microvascular hemodynamic glomerular model was developed to simulate blood flow and plasma filtration in an anatomically accurate rat glomerular capillary network. AA and EA resistances were adjusted to match glomerular hemodynamic data for control, Ang II-induced hypertension, and P2X1-blocked conditions. A blockade of the purinergic receptors reduced both afferent and efferent resistances, maintaining glomerular pressure at hypertensive levels but increasing blood flow and sheer stress significantly. Because glomerular pressure was maintained, hoop stress barely changed. Our results indicate that the activation of the purinergic system protects the glomerular microvasculature from elevated shear stress caused by increased blood flow that would occur in the absence of purinergic stimulation.
DOI: 10.3390/ijms26051928
Language: English
Subfield: Physiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
Award: G403849065
OpenAlex ID: W4407878644