Angiotensin II (ANG II) does not utilize the Janus Kinase 2/Signal Transducers of Activated Transcription (JAK/STAT) pathway in the molecular mechanism of blood pressure response to a low salt diet

Abstract

We recently reported that the JAK2 inhibitor AG490 prevented JAK/STAT pathway activation and hypertension during chronic iv. ANG II infusion. It is unknown, however, whether activation of JAK2 is required for ANG II to prevent blood pressure from decreasing in the physiologic response to low salt intake. This was tested by blocking JAK2 activation chronically in rats that were switched from normal‐ to low‐salt intake. Male SD rats with instrumented with artery and vein catheters for 24 hr/day mean arterial pressure (MAP) measurement and iv. infusions. Rats were maintained on a normal‐salt (NS) intake (~ 3 mEq/day), and after baseline measurements chronic iv. infusions of either: vehicle (Veh; saline), the AT1 receptor antagonist Losartan (LOS; 10 mg/kg/day) or AG490 (AG; 10 ng/kg/min) were begun. After a 4‐day control period, rats were switched to low‐salt intake (LS; 0.4 mEq/day), while Veh, LOS and AG infusions continued. There were no differences in MAP between any group under baseline conditions. During the control period, MAP averaged 93+4, 97+3 and 80+2 mm Hg in Veh, AG, and LOS groups, respectively. Switching to LS intake did not change MAP in Veh and AG rats (102+4 and 101+3 mm Hg, respectively); but MAP decreased significantly in LOS rats to 72+4 mm Hg by day 5. These data suggest that JAK2 activation is not involved in ANG II's role in the blood pressure response to LS intake. (HL74167 MWB; HL91177 AB)