The heterogeneity of dopamine-mediated vasodilation in human intrarenal arteries

Adequate renal perfusion is critical for maintaining kidney function, and its impairment contributes significantly to acute kidney injury (AKI) and related cardiovascular complications. Dopamine (DA) is clinically employed to improve renal perfusion, but its efficacy remains controversial due to paradoxical vasoconstriction at higher doses.

This study systematically evaluates DA-induced vasomotor responses in human intrarenal arteries and elucidates the underlying molecular mechanisms.

Human intrarenal artery segments, including interlobar (IA, ∼1 mm), arcuate (AA, ∼500 μm), and interlobular arteries (ILA, ∼200 μm), were analyzed using ex vivo tension assays, pharmacological interventions, RNA sequencing, and siRNA silencing to delineate segment-specific DA responses and molecular basis.

DA (1 nM-10 µM) consistently induces vasodilation across all human intrarenal arteries, challenging the conventional notion that "renal-dose DA" causes vasoconstriction. IA and AA segments exhibit more pronounced vasodilation than ILA, mediated by dopamine receptor D1 (DRD1)-dependent protein kinase A (PKA)-BK channel signaling. Specifically, higher expression and activity of the BK channel regulatory β-subunit (KCNMB1) in IA and AA accounted for their increased sensitivity to DA. Transcriptomic profiling further identified distinct molecular heterogeneity among IA, AA and ILA segments, reflecting their divergent physiological roles. In contrast, rodent intrarenal arteries respond to DA with vasoconstriction rather than dilation, due to the lack of the BK channel pore-forming α-subunit (KCNMA1), which shifts the balance toward α-adrenergic vasoconstriction.

Our study overturns the traditional paradigm of "renal-dose DA"-induced vasoconstriction, supports DRD1 agonism as a promising strategy for renal hypoperfusion, and emphasizes critical species differences that necessitate human-based validation in translational vascular research.