Effect of Fenoldopam on Cytosolic Nitric Oxide Production in Pkd1−⁄− Isolated Femoral Arteries in Response to Fluid Shear Stress Ex Vivo
Journal Title: Journal of Physiology and Pharmacology Advances - Year 2013, Vol 3, Issue 4
Abstract
Adult polycystic kidney disease (PKD) is a genetic disease resulted from mutation in polycystin 1 or 2 proved to be co-localized to endothelial primary cilia. Primary cilium is machanosensory organelle senses shear stress and mediates nitric oxide (NO) signaling. Hypertension is the main cardiovascular abnormality associated with PKD hypothesized to be caused by endothelial dysfunction resulted from defective NO production. To evaluate the effect of fenoldopam on mechanosensory function and NO production of endothelial cilia.Methods: ex vivo fluid shear stress on isolated femoral arteries from wild type and Pkd1−⁄− mice performed. Cytosolic NO measured as percent change in arteries incubated without (control) or with fenoldopam (10 μM; 16 hrs). Fenoldopam restored 80% of NO production and significantly (P<0.0001) elevated cytosolic NO in wild type (187.84±15.977% vs 300.6±15.311%) and Pkd (110.11±6.455% vs 151.17±5.753%) compared to control. Endothelial ciliary mechanosensory function and NO production restored in Pkd1−⁄− by fenoldopam in response to fluid shear stress.
Authors and Affiliations
S. H. Alkhateeb
Keywords
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