Purpose <p>Despite substantial advances in computational cardiovascular modeling, simplifying assumptions often overlook key compensatory mechanisms. To better capture physiological responses under pathological conditions, we incorporate two essential compensatory mechanisms—collateral circulation and arteriolar vasodilation—into a multiscale blood perfusion simulation framework.</p> Methods <p>Collateral vessels are stochastically generated to supply ischemic regions, with model parameters systematically varied to control vessel density, caliber, and spatial distribution. Arteriolar vasodilation is modeled to represent the combined response of vascular smooth muscle cells to local metabolic and hemodynamic stimuli. To assess their impact on perfusion, artificial stenoses are introduced into both an idealized geometry and a subject-specific cerebrovascular model.</p> Results <p>Simulation results across varying collateral configurations and vasodilation capacities demonstrate that perfusion enhancement from sub-resolution collateral vessels alone is limited and highly dependent on vessel caliber and density. In contrast, combining collateral flow with vasodilation produces a more pronounced improvement in tissue perfusion. These findings suggest that arteriolar vasodilation serves as the primary mechanism for ischemic compensation, with collateral circulation providing secondary support which is consistent with clinical observations.</p> Conclusion <p>The proposed methods enable multiscale blood flow simulations while accounting for the main autoregulatory mechanisms. The models have been verified using literature data and are shown to provide accurate results.</p>