Phosphoinositide 3‐kinase (PI3K) and mitogen activated protein kinase (MAPK) signaling in the paraventricular nucleus (PVN) in renal wrap hypertension

The PVN is a critical site for blood pressure maintenance. Moreover, PI3K and MAPK signaling cascades have been implicated in the pathogenesis of hypertension. Therefore, it was hypothesized that in the PVN there was increased PI3K and MAPK (ERK, JNK, and p38) signaling during the onset of renal wrap hypertension. The PVN was isolated from sham and hypertensive renal wrap rats on day 7 post surgery (MAP: 118 ±3 vs . 141 ± 8 mm Hg; p<0.05) for protein isolation and subsequent western analyses. There was significantly increased PVN pAkt from wrap compared to sham rats (3884 ± 534 vs. 7973 ± 1523 ADU; p<0.05). With regards to MAPK, during wrap hypertension there was decreased PVN pERK (3637 ± 584 vs. 1899 ± 604 ADU; p<0.05), increased JNK (1931 ± 870 vs. 3904 ± 358 ADU) (however no differences were found with regards to pJNK) and increased p38 (794 ± 242 vs. 1759 ± 317 ADU) in the PVN from wrap compared to sham rats. These results indicate there was a significant increase in the activation of the PI3K and p38 signaling pathways; however a decrease in activation of the ERK signaling cascade in the PVN during renal wrap hypertension. In conclusion, there are differences in MAPK and PI3K intracellular signaling occurring within the PVN during the onset of hypertension. Further studies will evaluate the physiological significance of these observed differences and whether they are critical in the etiology of hypertension. R00HL087927