Sympathoinhibition and vasodilation contribute to the acute hypotensive response of the superoxide dismutase mimic, MnTnBuOE-2-PyP5+, in hypertensive animals: BuOE's Hypotensive Response in Hypertensive Animals

Sarah L. Schlichte, Elizabeth J. Pekas, Taylor J. Bruett, Elizabeth A. Kosmacek, Bryan T. Hackfort, Jordan M. Rasmussen, Kaushik P. Patel, Song Young Park, Rebecca E. Oberley-Deegan, Matthew C. Zimmerman

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The pathogenesis of hypertension has been linked to excessive levels of reactive oxygen species (ROS), particularly superoxide (O2•−), in multiple tissues and organ systems. Overexpression of superoxide dismutase (SOD) to scavenge O2•− has been shown to decrease blood pressure in hypertensive animals. We have previously shown that MnTnBuOE-2-PyP5+ (BuOE), a manganese porphyrin SOD mimic currently in clinical trials as a normal tissue protector for cancer patients undergoing radiation therapy, can scavenge O2•− and acutely decrease normotensive blood pressures. Herein, we hypothesized that BuOE decreases hypertensive blood pressures. Using angiotensin II (AngII)-hypertensive mice, we demonstrate that BuOE administered both intraperitoneally and intravenously (IV) acutely decreases elevated blood pressure. Further investigation using renal sympathetic nerve recordings in spontaneously hypertensive rats (SHRs) reveals that immediately following IV injection of BuOE, blood pressure and renal sympathetic nerve activity (RSNA) decrease. BuOE also induces dose-dependent vasodilation of femoral arteries from AngII-hypertensive mice, a response that is mediated, at least in part, by nitric oxide, as demonstrated by ex vivo video myography. We confirmed this vasodilation in vivo using doppler imaging of the superior mesenteric artery in AngII-hypertensive mice. Together, these data demonstrate that BuOE acutely decreases RSNA and induces vasodilation, which likely contribute to its ability to rapidly decrease hypertensive blood pressure.

Original languageEnglish (US)
Article number100016
JournalAdvances in Redox Research
Volume3
DOIs
StatePublished - Dec 2021

Keywords

  • Hypertension
  • MnTnBuOE-2-PyP
  • Superoxide Dismutase
  • Sympathetic Nerve Activity
  • Vasodilation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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