Sympathoinhibition and vasodilation contribute to the acute hypotensive response of the superoxide dismutase mimic, MnTnBuOE-2-PyP5+, in hypertensive animals

Authors

Sarah L. Schlichte, University of Nebraska Medical Center
Elizabeth J. Pekas, University of Nebraska at OmahaFollow
Taylor J. Bruett, University of Nebraska Medical Center
Elizabeth A. Kosmacek, University of Nebraska Medical Center
Bryan T. Hackfort, University of Nebraska Medical Center
Jordan M. Rasmussen, University of Nebraska Medical Center
Kaushik P. Patel, University of Nebraska Medical Center
Song-young Park, University of Nebraska at OmahaFollow
Rebecca E. Oberley-Deegan, University of Nebraska Medical Center
Matthew C. Zimmerman, University of Nebraska Medical Center

Author ORCID Identifier

Park - https://orcid.org/0000-0001-8576-7531

Document Type

Article

Publication Date

9-8-2021

Publication Title

Advances in Redox Research

Volume

3

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.

Comments

This is an open access article licensed under the Creative Commons Attribution NonCommercial NoDerivatives license.

DOI: https://doi.org/10.1016/j.arres.2021.100016

Recommended Citation

Schlichte, Sarah L.; Pekas, Elizabeth J.; Bruett, Taylor J.; Kosmacek, Elizabeth A.; Hackfort, Bryan T.; Rasmussen, Jordan M.; Patel, Kaushik P.; Park, Song-young; Oberley-Deegan, Rebecca E.; and Zimmerman, Matthew C., "Sympathoinhibition and vasodilation contribute to the acute hypotensive response of the superoxide dismutase mimic, MnTnBuOE-2-PyP5+, in hypertensive animals" (2021). Health and Kinesiology Faculty Publications. 124.
https://digitalcommons.unomaha.edu/hperfacpub/124

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.