GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Dlitiazem inhibits the oxidative stress induced by angiotensin II through growth hormone secretagogue receptor type 1a in human umbilicus vein endothelial cells.
Zhou. Lingyun L; Yang. Meng M; Zuo. Shanru S; Guan. Xiaofeng X; Wang. Jianglin J; Chen. Qingjie Q; Zuo. Xiaocong X; Jia. Sujie S; Guo. Ren R
Key Findings
- Diltiazem reduces reactive oxygen species and boosts nitric oxide production in endothelial cells exposed to angiotensin II.
- Angiotensin II lowers eNOS (the enzyme that makes nitric oxide) and raises p47phox (a component of NADPH oxidase); diltiazem reverses both changes.
- The protective actions of diltiazem are partially blocked by the GHSR1a antagonist D‑Lys3‑GHRP‑6, indicating involvement of the GHSR1a pathway.
Practical Outcomes
- For biohackers, the data hint that activating GHSR1a (e.g., with GHRP‑6, an agonist) might support vascular health, but the evidence is limited to cell culture. Diltiazem’s endothelial benefits appear tied to this receptor, so combining it with GHSR‑activating peptides could be explored, though human studies are needed before any protocol changes.
Summary
The study shows that the blood‑pressure drug diltiazem can protect human vein cells from oxidative damage caused by angiotensin II, and that this protection depends partly on the growth‑ hormone secretagogue receptor (GHSR1a). Blocking GHSR1a with a peptide (D‑Lys3‑GHRP‑6) weakens diltiazem’s benefit, suggesting the receptor plays a role in the anti‑oxidant effect.
Abstract
Diltiazem has been used for post-transplant hypertension, but the mechanism underlying its protective effect of endothelial cells against angiotensin II (Ang II) - induced impairment remains unclear. Human umbilicus vein endothelial cells (HUVECs) were cultured and divided into seven groups: control, Ang II (10<sup>-6</sup>M), diltiazem (10<sup>-6</sup>M), [D-Lys3]-GHRP-6(25μM), diltiazem (10<sup>-6</sup>M)+Ang II (10<sup>-6</sup>M), losartan (10<sup>-6</sup>M)+Ang II (10<sup>-6</sup>M), [D-Lys3]-GHRP-6 (25μM) + Dil(10<sup>-6</sup>M)+Ang II (10<sup>-6</sup>M) groups. Nitric oxide (NO) production, intracellular reactive oxygen species (ROS) levels, protein and mRNA expressions of endothelial nitric oxide synthase (eNOS) and p47 phox subunit of NADPH were evaluated. Results indicated that pre- treatment with diltiazem significantly decreased the intracellular ROS levels and increased NO production. Treatment with 10<sup>-6</sup>M Ang II for 24h induced a significant decrease in the mRNA and protein levels of eNOS, which was significantly increased by the pre-incubated with diltiazem (10<sup>-6</sup>M). Treatment with 10<sup>-6</sup>M Ang II for 24h induced a significant increase in the mRNA and protein levels of p47 phox subunit of NADHP oxidase, which was significantly decreased by the pre-incubated with diltiazem. However, all of these protective roles of diltiazem were attenuated by pre-incubation of [D-Lys3]-GHRP-6. The results reveal that diltiazem inhibits the Ang II - induced oxidative stress in HUVECs, which may be partly mediated by GHSR1a.
Study Information
pubmed
2017
2017-02-17T00:00:00.000Z
10.1016/j.biopha.2017.02.022
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