Increased reactive oxygen species in rostral ventrolateral medulla contribute to neural mechanisms of hypertension in stroke-prone spontaneously hypertensive rats.

Kishi T, Hirooka Y, Kimura Y, Ito K, Shimokawa H, Takeshita A. Circulation. 2004 May 18;109(19):2357-62. Epub 2004 Apr 26. In this paper, the authors wanted to look at how baroreflex sensitivity (BRS) is impaired in cardiovascular disease (CVD) models, and how it can be linked to changes in reactive oxygen species (ROS). Their previous work had shown that by causing increased expression of manganese superoxide dismutase (MnSOD), they could reduce ROS and cause sympathoinhibition in hypertensive (HT) rats. However, that was kind of an acute study, so this time they wanted to look at BRS in HT rats, using a chronic redution in ROS via MnSOD overexpression. To do this, they injected the RVLM of spontaneously hypertensive rats (SHRs) with a construct causing expression of MnSOD. They found strong reductions in MAP and HR 5-9 days after injection, and a strong reduction in urinary norepinephrine at day 7. For the BRS, they found that the SHRs started with lower sensitivity than WKY-MnSOD controls, but became more sensitive after transfection (days 5-8). WKY-MnSODs did not demonstrate this increase in sensitivity, nor did LacZ-SHR controls. I have a bit of confusion about this paper... I'm honestly not sure exactly how they measured BRS, partially because I didn't look up the two papers describing how BRS is calculated. I admit, not knowing this is kind of a big hole in my interpretation of the paper. In my defense, the two papers they referenced on the technique seem to be calculating BRS in humans, and they never referenced any papers showing how it was done in rats, so I can't yet be really confident about the technique. I dug up a couple of this group's other papers and didn't see it in those ones either, so I might have to go look in to this one more, or consult our resident expert. I'm also a little confused about how all of the effects peaked at one week before returning to baseline levels, as soon as day 9. I know that viral expression isn't always permament, but is 7 days "chronic?" Is there a combined effect of the transfection failing AND some kind of compensation happening to maintain the MAP/HR/BRS? The levels of MnSOD were only shown at days 0,7, and 21... I'd like to know if their expression graphs match the effects - that might answer part of this question. -DH