Polycystin-1 Does Not Regulate The Contractility of Systemic Artery Smooth Muscle Cells

Polycystin 1 (PKD1), a large surface protein encoded by the Pkd1 gene, is expressed in several cell types, including arterial smooth muscle cells. A previous study, which used SM22α as a non-selective Cre driver to generate Pkd1 knockout mice, proposed that PKD1 in smooth muscle cells is a pressure sensor which regulates mesenteric artery contractility (Sharif-Naeini et al, Cell 2008). To investigate the vascular significance of PKD1, we used Myh11 as a Cre driver to generate tamoxifen-inducible, smooth muscle cell-specific Pkd1 knockout ( Pkd1 smKO) mice. PKD1 expression, arterial contractility and blood pressure were compared in Pkd1 fl/fl control and Pkd1 smKO mice. Western blotting and immunofluorescence imaging experiments demonstrated that PKD1 was expressed in mesenteric artery smooth muscle cells of Pkd1 fl/fl mice but absent in cells of Pkd1 smKO mice. Intravascular pressures between 10 and 125 mmHg stimulated similar vasoconstrictions (myogenic tone) in resistance-size mesenteric and gastrocnemius arteries of Pkd1 fl/fl and Pkd1 smKO mice. Membrane depolarization (60 mM K + ) or the receptor-mediated vasoconstrictor agonists phenylephrine and angiotensin II also similarly constricted pressurized (80 mmHg) mesenteric arteries of Pkd1 fl/fl and Pkd1 smKO mice. Acetylcholine (10 μM), an endothelium dependent vasodilator, similarly dilated Pkd1 fl/fl and Pkd1 smKO mouse mesenteric arteries. Vasoactive responses of Pkd1 fl/fl and Pkd1 smKO mice were similar regardless of whether experiments were performed 14 or 28 days after PKD1 knockout. Consistent with these results, blood pressure and heart rate were also similar in Pkd1 fl/fl and Pkd1 smKO mice. These data indicate that PKD1 is expressed in systemic artery smooth muscle cells, but it does not contribute to pressure-, depolarization- or agonist-induced vasoconstriction, or regulate systemic blood pressure. This research was funded by grant NHLBI HL158846, HL155180, and HL166411. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.