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.
Receptor downregulated in hypertensionGHS-R1a levels were decreased in both brain and kidneys of spontaneously hypertensive rats compared to normal controls
What the researchers 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.
Why it 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 numbers in context
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 the study worked
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.
Who was studied
Wistar (normotensive) and SHR (spontaneously hypertensive) rats
What this study cannot 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.
How to read the evidence
Preliminary — well-designed rat study but observational regarding receptor levels. Cannot establish whether receptor loss causes or results from hypertension.
When this study was published
Published in 2020; the cardiovascular roles of the ghrelin system continue to be investigated.
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.
Questions still open
- 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?
Common questions
What is GHS-R1a and how does it relate to MK-677?
Could MK-677 help with high blood pressure?
Read the original research
Brain and kidney GHS-R1a underexpression is associated with changes in renal function and hemodynamics during neurogenic hypertension.
Molecular and cellular endocrinology, 518, 110984
Citation
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