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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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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Cureus
2021
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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. |
format | Online Article Text |
id | pubmed-8655868 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cureus |
record_format | MEDLINE/PubMed |
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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