Authors
Zhugang Chu, Qidi Zhai, Liming Lu, Maik Gollasch, Dmitry Tsvetkov, Rong Dong, S R Wayne Chen, Gang Fan, Guangheng Luo, Mario Kassmann
Published in
British journal of pharmacology. Oct 13, 2026. Epub Oct 13, 2026.
Abstract
Coordinated peristalsis between the renal pelvis and ureter is critical for effective urine transport. However, intraluminal pressure impact on upper urinary tract (UUT) contractility and pharmacologic responsiveness remains poorly understood due to absence of suitable investigative methods.
This study introduces the first application of high-resolution pressure myography to UUT, establishing a novel ex vivo platform enabling simultaneous, intraluminal pressure-controlled local measurement of renal pelvic contraction frequency and amplitude and ureteral inner diameter, outer diameter, and wall thickness. To define contribution of specific Ca2+ signaling pathways, we pharmacologically examined Cav1.2 L-type, Cav3.x T-type, and ryanodine receptor channels, as well as sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and neuronal involvement.
Elevating intraluminal pressure from 4 to 20 mmHg increased renal pelvic contraction frequency, while amplitude markedly decreased. Ureteral wall thinning was the main structural adaptation. Nifedipine reduced renal pelvic contraction amplitude and frequency and suppressed ureter peak contraction, all with reduced efficacy under high-pressure conditions. Ni2+ affected renal pelvic contractility only at high concentrations and had no effect on ureteral dynamics. Ryanodine did not alter measured parameters, and Na+ and N-type Ca2+ channels were not involved.
High-resolution pressure myography reveals pressure-dependent local contractile and geometric responses in UUT, including altered contraction dynamics, ureteral geometric remodeling, and specific Ca2+ channel contributions. Cav1.2 channels modulate both amplitude and frequency, with wall thinning as principal acute structural adaptation. Reduced drug efficacy at high pressure highlights necessity to investigate possible pressure-adapted therapies in obstructive uropathy.
PMID:
42865197
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.
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