Involvement of activation of Janus kinase (JAK)2 in the mechanisms utilized by Norepinephrine (NE) to cause hypertension.

Angiotensin II (ANG II) utilizes activation of JAK2 signaling pathways to cause hypertension. It is unknown if NE is dependent on JAK2 pathway activation to increase in blood pressure. We hypothesized that NE requires JAK2 activation to increase blood pressure. Male Sprague‐Dawley rats were catheterized via abdominal aorta and femoral vein to chronically measure blood pressure and infuse drugs. NE and ANG II were infused for 18 days and tissues harvested for western blot analysis. Mean arterial pressure (MAP) increased significantly in the ANG II and NE infused rats. There was a significant increase in phosphorylation levels of JAK2 as measured by Western blot analysis in the ANG II (10 ng/kg/min) and NE (2.8 mg/kg/day) treated rats than the saline controls. Infusion of JAK2 inhibitor AG490 (10 ng/kg/min) did not inhibit initial NE‐induced increases in blood pressure but did reduce NE's ability to maintain sustained increases in MAP. To determine if NE also requires a vascular component that involves JAK2 activation we utilized ex vivo myograph recordings. Using the thoracic aorta from naïve male rats we tested whether NE requires JAK2 activation for vascular contraction. We found that NE‐induced contraction was not significantly reduced by treatment with the JAK2 inhibitor AG490. These data suggest that NE and ANG II both increase and utilize JAK2 activation but via different mechanisms. (ABB NHLBI R00; MWB NHLBI R01).