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Paradoxical Increase in Body Mass Induced by Beta-Guanidinopropionic Acid in Juvenile Spontaneously Hypertensive Rats

Background The adenosine triphosphate (ATP) regenerating enzyme creatine kinase (CK) is intimately involved in blood pressure generation. Consequently, the creatine transporter and CK inhibitor beta-guanidinopropionic acid (GPA) successfully reduced blood pressure in 16-week-old spontaneously hypert...

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Autor principal: Brewster, L M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cureus 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8655868/
https://www.ncbi.nlm.nih.gov/pubmed/34925996
http://dx.doi.org/10.7759/cureus.19394
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author Brewster, L M
author_facet Brewster, L M
author_sort Brewster, L M
collection PubMed
description Background The adenosine triphosphate (ATP) regenerating enzyme creatine kinase (CK) is intimately involved in blood pressure generation. Consequently, the creatine transporter and CK inhibitor beta-guanidinopropionic acid (GPA) successfully reduced blood pressure in 16-week-old spontaneously hypertensive rats (SHR), but GPA may cause growth retardation in juvenile mammals. This report considers a serendipity observation of paradoxical growth increase after using GPA to prevent hypertension in three-week-old SHR. Methods Implementing the “Animal Research: Reporting of In Vivo Experiments” (ARRIVE) guideline, male, three-week-old spontaneously hypertensive rats (N=22) were randomly assigned to standard soy-based (creatine-free) chow with GPA 0.1% vs control chow during four weeks (primary, t=4w) or six weeks of treatment (t=6w). Blood pressure measured by the tail-cuff method was the main outcome. Other outcomes included body mass and contractility characteristics of isolated arteries. Results  Body mass at baseline was 28.4 (SE 0.71) g (n=22). With similar food intake/100 gram animal in both groups, GPA-treated rats (n=11) developed a strikingly larger body size and mass: t=4w, GPA 110.4 g (3.7) vs controls (n=11) 65.0 g (4.8) (+69.8%; p<0.001); t=6w, GPA 154.3 (4.7) vs controls 68.0 (4.7) g. There were no significant differences in cardiovascular parameters including blood pressure. Discussion An unexpected increase in body mass and size without concurrent blood pressure increase was observed in juvenile SHR on GPA vs control soy-based chow. It is speculated that the partial creatine agonist activity of GPA contributed to these effects. Further studies are needed to confirm these findings and better understand the impact of modulating energy metabolism in juvenile hypertension-prone mammals.
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spelling pubmed-86558682021-12-17 Paradoxical Increase in Body Mass Induced by Beta-Guanidinopropionic Acid in Juvenile Spontaneously Hypertensive Rats Brewster, L M Cureus Cardiology Background The adenosine triphosphate (ATP) regenerating enzyme creatine kinase (CK) is intimately involved in blood pressure generation. Consequently, the creatine transporter and CK inhibitor beta-guanidinopropionic acid (GPA) successfully reduced blood pressure in 16-week-old spontaneously hypertensive rats (SHR), but GPA may cause growth retardation in juvenile mammals. This report considers a serendipity observation of paradoxical growth increase after using GPA to prevent hypertension in three-week-old SHR. Methods Implementing the “Animal Research: Reporting of In Vivo Experiments” (ARRIVE) guideline, male, three-week-old spontaneously hypertensive rats (N=22) were randomly assigned to standard soy-based (creatine-free) chow with GPA 0.1% vs control chow during four weeks (primary, t=4w) or six weeks of treatment (t=6w). Blood pressure measured by the tail-cuff method was the main outcome. Other outcomes included body mass and contractility characteristics of isolated arteries. Results  Body mass at baseline was 28.4 (SE 0.71) g (n=22). With similar food intake/100 gram animal in both groups, GPA-treated rats (n=11) developed a strikingly larger body size and mass: t=4w, GPA 110.4 g (3.7) vs controls (n=11) 65.0 g (4.8) (+69.8%; p<0.001); t=6w, GPA 154.3 (4.7) vs controls 68.0 (4.7) g. There were no significant differences in cardiovascular parameters including blood pressure. Discussion An unexpected increase in body mass and size without concurrent blood pressure increase was observed in juvenile SHR on GPA vs control soy-based chow. It is speculated that the partial creatine agonist activity of GPA contributed to these effects. Further studies are needed to confirm these findings and better understand the impact of modulating energy metabolism in juvenile hypertension-prone mammals. Cureus 2021-11-09 /pmc/articles/PMC8655868/ /pubmed/34925996 http://dx.doi.org/10.7759/cureus.19394 Text en Copyright © 2021, Brewster et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Cardiology
Brewster, L M
Paradoxical Increase in Body Mass Induced by Beta-Guanidinopropionic Acid in Juvenile Spontaneously Hypertensive Rats
title Paradoxical Increase in Body Mass Induced by Beta-Guanidinopropionic Acid in Juvenile Spontaneously Hypertensive Rats
title_full Paradoxical Increase in Body Mass Induced by Beta-Guanidinopropionic Acid in Juvenile Spontaneously Hypertensive Rats
title_fullStr Paradoxical Increase in Body Mass Induced by Beta-Guanidinopropionic Acid in Juvenile Spontaneously Hypertensive Rats
title_full_unstemmed Paradoxical Increase in Body Mass Induced by Beta-Guanidinopropionic Acid in Juvenile Spontaneously Hypertensive Rats
title_short Paradoxical Increase in Body Mass Induced by Beta-Guanidinopropionic Acid in Juvenile Spontaneously Hypertensive Rats
title_sort paradoxical increase in body mass induced by beta-guanidinopropionic acid in juvenile spontaneously hypertensive rats
topic Cardiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8655868/
https://www.ncbi.nlm.nih.gov/pubmed/34925996
http://dx.doi.org/10.7759/cureus.19394
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