Hot off the press!! Splanchnic sympathetic nerves in the development of mild DOCA-salt hypertension.

Hi everyone, sorry for the gap since my last post, but I hope I can make up for it with this exciting new paper from our friends down the road at Michigan State.

Recent work from Greg Fink's lab (last author) and others has highlighted the importance of examining splanchnic sympathetic activity in the development and/or maintanance of hypertension. For example, experimental hypertension induced in rats using exogenous angiotensin II and a high salt diet is characterized by differential sympathetic responses depending on which "sympathetic regions", including splanchnic, are examined. In that model, renal nerve activity is decreased and lumbar nerve activity remains unchanged as measured by chronic nerve recordings in conscious rats. If the splanchnic sympathetic bed is denervated by removing the celiac ganglia (CGx) in the same model, blood pressure falls dramatically, suggesting that sympatehtic activity to the splanchnic bed is increased.
In this new study, they examine the role of the splanchnic bed in another clinically relevant model of hypertension, the DOCA-salt model. Similar to the ANGII-salt model, it appears that the combination of high salt with overexposure to a blood pressure regulating hormone, in this case the aldosterone-like molecule deoxycorticosterone acetate (DOCA), produces significant hypertension.
The lead author implanted a long-term release DOCA pellet in rats at the same time as implanting a radiotelemeter to measure arterial pressure chronically. Some rats were subjected to  CGx and some underwent the same surgery except not denervated. Over a period of two weeks to a month, blood pressure significantly increased in both groups, but the increase was significantly attenuated in CGx rats. At the end of the experiment, tissue supplied via the spalnchnic circulation was harvested and analyzed for norepinephrine (NE) content. NE was markedly diminished in the sampled tissues, indicating that CGx was effective. Additionally, the lead author infused radiolabeled NE into the rats until it reached steady state concentrations, then simultaneously sampled arterial and venous splanchnic blood for radiolabeled and endogenous NE levels. A calculation of the differences between arterial and venous values of radiolabeled and endogenous NE indicates how much endogenous NE is has been used by sympathetic nerve terminals as a neurotransmitter and then "spilled over" into venous blood. This procedure is a way to measure NE handling in specific tissues, with increased NE spillover indicating increased sympathetic outflow to the tissue. They found that whole-body NE spillover and NE plasma levels were decreased in CGx during the control period, but not during DOCA-salt. Similar findings were observed with splanchnic NE spillover.
The data indicate that the splanchnic bed certainly contributes to hypertension in this model but is not wholly responsible for it. In addition, splanchnic SNA does not appear to be increased in this model when assessed by the NE spillover method. Thus, it is possible that, in this model, increased reactivity of the splanchnic vasculature decreased arterial and venous compliance and leads to increased central arterial pressure.

-Nick