AI Article Synopsis
- The study investigates how the PI3K signaling pathway affects blood pressure in hypertensive rats compared to normal rats, focusing on the nucleus tractus solitarii (NTS).
- Microinjecting PI3K inhibitors like wortmannin and LY294002 into the NTS of hypertensive rats led to significant decreases in mean arterial pressure (MAP) and improvements in baroreflex sensitivity (BRS) and heart rate variability (HRV).
- In contrast, the same injections did not have any effect in control rats, highlighting the role of the PI3K pathway in regulating blood pressure in genetically altered hypertensive rats.
Article Abstract
The phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathway in brain of spontaneously hypertensive rats, but not Wistar-Kyoto (WKY) rats, contributes to elevated mean arterial pressure (MAP). The role of PI3K in the regulation of blood pressure or autonomic function in the nucleus tractus solitarii (NTS) is yet to be established in other Ang II-dependent models of hypertension. Thus, we microinjected PI3K inhibitors, wortmannin or LY294002, into the NTS, and measured MAP, baroreflex sensitivity (BRS) for heart rate (HR) control, and HR variability (HRV) in mRen2.Lewis congenic and (mRen2)27 transgenic rats. Bilateral NTS microinjections of wortmannin (100 nmol/L; 50 nL) reduced MAP in (mRen2)27 and mRen2.Lewis rats (33 ± 5 mm Hg, n = 7, and 32 ± 6 mm Hg, n = 9, respectively) for approximately 90 minutes. Spectral and sequence analysis showed improvements in spontaneous BRS and HRV (50%-100%) after treatment in both hypertensive strains. Injections of wortmannin into NTS of Hannover Sprague-Dawley or Lewis control rats failed to alter MAP, BRS, or HRV. In mRen2.Lewis, but not in control Lewis rats, LY294002 (50 μmole/L) reduced MAP and increased BRS and HRV similar to wortmannin. Thus, the pharmacologic blockade of the PI3K signaling pathway in NTS reveals an important contribution to resting MAP and BRS in rats with overexpression of the Ren2 gene.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188661 | PMC |
| http://dx.doi.org/10.1097/FJC.0b013e31822555ca | DOI Listing |
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