Chronic administration of hexarelin attenuates cardiac fibrosis in the spontaneously hypertensive rat.
Xu. Xiangbin X; Ding. Fan F; Pang. Jinjiang J; Gao. Xue X; Xu. Rong-Kun RK; Hao. Wei W; Cao. Ji-Min JM; Chen. Chen C
Key Findings
- Hexarelin reduced interstitial and perivascular collagen deposition and overall heart collagen content in hypertensive rats.
- Treatment increased activity of collagen‑degrading enzymes (MMP‑2 and MMP‑9) and lowered the inhibitor TIMP‑1, suggesting enhanced collagen breakdown.
- Hexarelin lowered systolic blood pressure, left‑ventricular hypertrophy, and diastolic dysfunction, and these effects were blocked by a GHS‑R antagonist.
Practical Outcomes
- For biohackers, this study shows that hexarelin can act as an anti‑fibrotic and blood‑pressure‑lowering agent in an animal model, hinting at possible heart‑protective benefits. However, because the data are from rats and involve a specific receptor mechanism, it isn’t ready for direct human dosing or protocol recommendations yet. Keep an eye on future human trials before considering self‑administration.
Summary
In a rat model of high blood pressure, giving the peptide hexarelin for five weeks lowered heart scarring, reduced heart muscle thickening, improved heart function, and lowered blood pressure. These benefits depended on the peptide’s specific receptor, because blocking the receptor stopped the effects.
Abstract
Cardiac fibrosis is a hallmark of heart disease and plays a vital role in cardiac remodeling during heart diseases, including hypertensive heart disease. Hexarelin is one of a series of synthetic growth hormone secretagogues (GHSs) possessing a variety of cardiovascular effects via action on GHS receptors (GHS-Rs). However, the role of hexarelin in cardiac fibrosis in vivo has not yet been investigated. In the present study, spontaneously hypertensive rats (SHRs) were treated with hexarelin alone or in combination with a GHS-R antagonist for 5 wk from an age of 16 wk. Hexarelin treatment significantly reduced cardiac fibrosis in SHRs by decreasing interstitial and perivascular myocardial collagen deposition and myocardial hydroxyproline content and reducing mRNA and protein expression of collagen I and III in SHR hearts. Hexarelin treatment also increased matrix metalloproteinase (MMP)-2 and MMP-9 activities and decreased myocardial mRNA expression of tissue inhibitor of metalloproteinase (TIMP)-1 in SHRs. In addition, hexarelin treatment significantly attenuated left ventricular (LV) hypertrophy, LV diastolic dysfunction, and high blood pressure in SHRs. The effect of hexarelin on cardiac fibrosis, blood pressure, and cardiac function was mediated by its receptor, GHS-R, since a selective GHS-R antagonist abolished these effects and expression of GHS-Rs was upregulated by hexarelin treatment. In summary, our data demonstrate that hexarelin reduces cardiac fibrosis in SHRs, perhaps by decreasing collagen synthesis and accelerating collagen degradation via regulation of MMPs/TIMP. Hexarelin-reduced systolic blood pressure may also contribute to this reduced cardiac fibrosis in SHRs. The present findings provided novel insights and underscore the therapeutic potential of hexarelin as an antifibrotic agent for the treatment of cardiac fibrosis.
Study Information
pubmed
2012
2012-07-27T00:00:00.000Z
10.1152/ajpheart.00257.2011
32
43