Ghrelin Receptor Downregulation in Brain and Kidneys May Contribute to High Blood Pressure
Spontaneously hypertensive rats had reduced ghrelin receptor (GHS-R1a) levels in brain and kidneys, and ghrelin treatment lowered blood pressure and improved kidney blood flow in these animals.
Quick Facts
What This Study Found
GHS-R1a protein was decreased in brain areas and kidneys of hypertensive rats. Ghrelin reduced arterial pressure and increased renal artery conductance in SHR. GHS-R1a antagonism altered renal electrolyte handling in normal but not hypertensive rats, suggesting impaired receptor function in hypertension.
Key Numbers
GHS-R1a reduced in brain and kidneys of SHR; ghrelin reduced BP and increased renal artery conductance in SHR; MK-677 changed osmolarity parameters
How They Did This
Compared Wistar (normal) and SHR (hypertensive) rats. Systemically injected ghrelin, MK-677, GHS-R1a antagonist PF04628935, or combinations. Metabolic cage studies measuring urine output and electrolytes. Assessed renal hemodynamics and vasomotion. Western blot for GHS-R1a levels in brain, aorta, renal artery, renal cortex, and medulla.
Why This Research Matters
Hypertension is the leading cause of kidney disease and cardiovascular death. If ghrelin receptor downregulation contributes to hypertensive kidney damage, it could represent a new therapeutic target.
The Bigger Picture
This study connects the ghrelin/growth hormone secretagogue system to blood pressure regulation and kidney function, suggesting the metabolic hormone ghrelin has cardiovascular roles beyond appetite and growth hormone release.
What This Study Doesn't Tell Us
Animal model of genetic hypertension — may not reflect human essential hypertension. Ghrelin receptor levels measured at a single time point. Causal relationship between receptor downregulation and hypertension not established.
Questions This Raises
- ?Is ghrelin receptor expression reduced in kidneys of human hypertensive patients?
- ?Could ghrelin or MK-677 be used as adjunctive treatments for hypertension-related kidney dysfunction?
- ?Does the receptor downregulation cause hypertension or result from it?
Trust & Context
- Key Stat:
- Receptor downregulated in hypertension GHS-R1a levels were decreased in both brain and kidneys of spontaneously hypertensive rats compared to normal controls
- Evidence Grade:
- Preliminary — well-designed rat study but observational regarding receptor levels. Cannot establish whether receptor loss causes or results from hypertension.
- Study Age:
- Published in 2020; the cardiovascular roles of the ghrelin system continue to be investigated.
- Original Title:
- Brain and kidney GHS-R1a underexpression is associated with changes in renal function and hemodynamics during neurogenic hypertension.
- Published In:
- Molecular and cellular endocrinology, 518, 110984 (2020)
- Authors:
- Sales da Silva, Elder, Ferreira, Patrícia Maria, Castro, Carlos Henrique(2), Pacheco, Lilian Fernanda, Graziani, Daniel, Pontes, Carolina Nobre Ribeiro, Bessa, Amanda de Sá Martins de, Fernandes, Erika, Naves, Lara Marques, Ribeiro, Larissa Cristina Dos Santos, Mendonça, Michelle Mendanha, Gomes, Rodrigo Mello, Pedrino, Gustavo Rodrigues, Ferreira, Reginaldo Nassar, Xavier, Carlos Henrique
- Database ID:
- RPEP-05105
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
What is GHS-R1a and how does it relate to MK-677?
GHS-R1a (growth hormone secretagogue receptor) is the receptor that ghrelin, MK-677, and other growth hormone-releasing peptides bind to. MK-677 is a synthetic agonist that activates this receptor to stimulate growth hormone release and appetite.
Could MK-677 help with high blood pressure?
This study suggests ghrelin receptor activation may improve kidney blood flow and lower blood pressure in hypertensive animals. However, this is preliminary animal data and MK-677 is not approved for treating hypertension.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-05105APA
Sales da Silva, Elder; Ferreira, Patrícia Maria; Castro, Carlos Henrique; Pacheco, Lilian Fernanda; Graziani, Daniel; Pontes, Carolina Nobre Ribeiro; Bessa, Amanda de Sá Martins de; Fernandes, Erika; Naves, Lara Marques; Ribeiro, Larissa Cristina Dos Santos; Mendonça, Michelle Mendanha; Gomes, Rodrigo Mello; Pedrino, Gustavo Rodrigues; Ferreira, Reginaldo Nassar; Xavier, Carlos Henrique. (2020). Brain and kidney GHS-R1a underexpression is associated with changes in renal function and hemodynamics during neurogenic hypertension.. Molecular and cellular endocrinology, 518, 110984. https://doi.org/10.1016/j.mce.2020.110984
MLA
Sales da Silva, Elder, et al. "Brain and kidney GHS-R1a underexpression is associated with changes in renal function and hemodynamics during neurogenic hypertension.." Molecular and cellular endocrinology, 2020. https://doi.org/10.1016/j.mce.2020.110984
RethinkPeptides
RethinkPeptides Research Database. "Brain and kidney GHS-R1a underexpression is associated with ..." RPEP-05105. Retrieved from https://rethinkpeptides.com/research/sales-2020-brain-and-kidney-ghsr1a
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.