Overexpressed C1q-TNF-related protein-9 in hypothalamic paraventricular nucleus ameliorates hypertension through modulating cytokines and attenuating oxidative stress in spontaneously hypertensive rats

The adipocytokine C1q/TNF-related protein 9 (CTRP9) was recently reported to have multiple protective effects on cardiac and cardiovascular function. However, the exact role of CTRP9 in the progression of hypertension remains unclear. This study was designed to determine whether overexpressed CTRP9 in hypothalamic paraventricular nucleus (PVN) attenuates hypertension through modulating pro-inflammatorycytokines and attenuating oxidative stress in spontaneously hypertensive rats (SHRs). Our data on enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction showed that CTRP9 mRNA and protein content were markedly downregulated in SHRs. SHRs had higher mean arterial pressure (MAP) and plasma norepinephrine (NE). These rats also had higher levels of tumor necrosis factor alpha (TNF)-α, interleukin-1beta (IL-1β), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and higher gp 91phox , gp 47phox (subunits of NAD (P)H oxidase) expression and superoxide production in PVN. Bilateral PVN microinjection of adeno-associated virus (AAV)-CTRP9 significantly attenuated MAP and NE, also reduced the expressions of TNF-α, IL-1β, IL-6, MCP-1, gp 91phox and gp 47phox in PVN of SHRs, but not in WKY rats. The mRNA expression of TNF-α, IL-1β, IL-6, MCP-1, gp 91phox and gp 47phox are in accordance with their protein expression. In conclusion, CTRP9 in PVN ameliorated hypertension may through modulating cytokines and attenuating oxidative stress in spontaneously hypertensive rats.