Smooth muscle cell polycystin 1 (PKD1) is dispensable for physiological regulation of arterial contractility

Polycystin 1 (PKD1) is a large transmembrane protein expressed by the Pkd1 gene. Previous data obtained using germline non-specific knockout mice suggested that PKD1 regulates arterial smooth muscle cell contractility. Here, we generated tamoxifen-inducible, smooth muscle cell-specific (Myh11-CreER^T2) Pkd1 knockout (Pkd1 smKO) mice to further investigate the functional significance of PKD1 in arterial myocytes. Reverse-transcription polymerase chain reaction, western blotting and immunofluorescence imaging demonstrated that PKD1 message and protein were expressed in arterial myocytes of male control (Pkd1^fl/fl) mice but absent in arterial myocytes of Pkd1 smKO mice. Polycystin 2 (PKD2), a transient receptor potential channel which can couple to PKD1, was similarly expressed in arteries of Pkd1^fl/fl and Pkd1 smKO mice. Kidney anatomy and glomerular and proximal tubule sizes were unaltered in Pkd1 smKO mice. Intravascular pressures of between 10 and 125 mmHg similarly constricted resistance-size mesenteric and gastrocnemius muscle arteries of Pkd1^fl/fl and Pkd1 smKO mice, regardless of whether experiments were performed 14 or 28 days after tamoxifen administration. Membrane depolarization (60 mm K⁺), phenylephrine and angiotensin II also comparably constricted arteries of Pkd1^fl/fl and Pkd1 smKO mice. Acetylcholine, an endothelium-dependent vasodilator, stimulated equivalent dilatation in Pkd1^fl/fl and Pkd1 smKO mouse arteries. Consistent with these results, blood pressure and heart rate were similar in Pkd1^fl/fl and Pkd1 smKO mice. In summary, these data indicate that PKD1 is expressed in systemic artery myocytes, but it does not contribute to pressure-, depolarization- or agonist-induced vasoconstriction, or regulate blood pressure. KEY POINTS: Polycystin 1 (PKD1) is a large membrane protein expressed in several cell types, including vascular smooth muscle cells. Previous data obtained using germline non-specific knockout mice proposed that PKD1 regulates arterial smooth muscle cell contractility. We generated tamoxifen-inducible smooth muscle cell-specific PKD1 knockout mice to further investigate the regulation of arterial smooth muscle cell contractility by PKD1. Our data show that PKD1 is expressed in smooth muscle cells, but it does not contribute to intravascular pressure-, agonist- or depolarization-induced constriction, nor does its knockout alter endothelial cell-dependent vasodilatation in resistance-size systemic arteries of male mice. Smooth muscle cell PKD1 does not regulate blood pressure or heart rate. We conclude that PKD1 is dispensable for physiological regulation of arterial smooth muscle cell contractility.