title: The functional role of PI3K in maintenance of blood pressure and baroreflex suppression in (mRen2)27 and mRen2.Lewis rat.
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.
authors.affiliation: Department of Life Sciences and Biomedical Research Infrastructure Center, Winston-Salem State University, Winston-Salem, NC, USA.
authors.forename: Exazevia M
authors.initials: EM
authors.lastname: Logan
authors.forename: Azeez A
authors.initials: AA
authors.lastname: Aileru
authors.forename: Hossam A
authors.initials: HA
authors.lastname: Shaltout
authors.forename: David B
authors.initials: DB
authors.lastname: Averill
authors.forename: Debra I
authors.initials: DI
authors.lastname: Diz
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D006339:Heart Rate / Q000502:physiology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D011917:Rats, Inbred Lew; D055647:Rats, Transgenic; D012083:Renin / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002867:Chromones; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012083:Renin; D000077191:Wortmannin; C473112:Ren2 protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one