Abstract 063: Role of Ribosomal S6 Kinase 2 in Vascular Myogenic Tone and Blood Pressure Regulation

• DOI: 10.1161/hyp.68.suppl_1.063
• Publication Date: 2021-06-21T16:51:13Z
• Authors: Mykhaylo Artamonov; Miranda Good; Ko Momotani; Brant Isakson; Robert Carey; Thu H Le; Avril V Somlyo
• Keywords: Myosin-light-chain phosphatase; Phenylephrine; Contractility; Ribosomal s6 kinase; Mesenteric arteries

Smooth muscle (SM) contractile force is generated through phosphorylation of the myosin regulatory light chain (RLC20) by kinase. However, emerging evidence also suggests that additional Ser/Thr kinases may contribute to pathways regulate SM contractility. Recently, we published 90 kDa ribosomal S6 kinase (RSK), extensively studied in cancers epithelial origin, a major new player regulation RSKs are unusual having two catalytic domains separated linker multiple sites and activated cascade ERK phosphorylations PDK, which phosphorylates RSK at Ser227 resulting transition fully active enzyme. The thromboxane agonist, U46619 leads activation ERK1/2 PDK1 SM. We find 4 th order mesenteric arteries significantly more dilated pressure 80 mm Hg Rsk2 -/- mice compared wild-type (WT) (2.0±0.8 vs 12.8±4.5 %, p <0.05, respectively). response dose-dependent phenylephrine stimulation smaller absence RSK2, <0.0001 two-way ANOVA, while EC50 for contractions did not differ. Using isolated arcades vessels, RLC20 phosphatase subunit (PDK site) Thr 577 (ERK increased with 30secs following an increase intraluminal induce myogenic tone development. Mean baseline systolic blood (SBP, mmHg) was lower animals (WT=107.4±1.6 RSK2 =95.8±2.2, n=23, p< 0.0002). In view SBP animals, examined potential role signaling kidney, since known phosphorylate NHE3. By immunohistochemistry, show first time expression human kidney tubules. Lithium excretion, moles/kg/day, Rsk2-/- WT (21.7±3.7 48.6±7.9, respectively), indicative defective renal Na + reabsorption. Taken together, vascular novel mechanism contractility BP. be selective target hypertension.