GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Inotropic and lusitropic effects of ghrelin and their modulation by the endocardial endothelium, NO, prostaglandins, GHS-R1a and KCa channels.
Soares. João-Bruno JB; Rocha-Sousa. Amândio A; Castro-Chaves. Paulo P; Henriques-Coelho. Tiago T; Leite-Moreira. Adelino F AF
Key Findings
- Ghrelin dose‑dependently reduces active tension and the speed of contraction (negative inotropic effect) in rat heart muscle.
- Ghrelin also speeds up relaxation (negative lusitropic effect) and causes an earlier onset of relaxation.
- These cardiac effects are independent of the GHS‑R1a receptor and are partly mediated by KCa channels, prostaglandins, and nitric oxide.
Practical Outcomes
- If you use GHRP‑6 to boost growth hormone, be aware that the resulting rise in ghrelin could lower heart contractility, especially at higher doses. Monitoring heart function and avoiding chronic high‑dose regimens may reduce potential cardiac side‑effects. Blocking GHS‑R1a won’t prevent these effects, so safety considerations should focus on overall ghrelin exposure rather than receptor antagonism.
Summary
The study shows that ghrelin, the hormone released when you take GHRP‑6, makes heart muscle contract less strongly and relax faster in rats. These heart‑weakening effects happen at very low concentrations, work the same in normal and enlarged hearts, and are not stopped by blocking the usual ghrelin receptor, but involve other pathways like potassium channels, prostaglandins and nitric oxide.
Abstract
Contractile effects of ghrelin (10(-9) to 10(-6) M) were tested in rat papillary muscles of normal (n = 50) and hypertrophic (n = 16) right ventricles (RV). RV hypertrophy was induced by pulmonary hypertension using monocrotaline. In normal muscles, ghrelin was added either alone (n = 9) or after pre-treatment with indomethacin (cycloxygenase inhibitor, 10(-5) M; n = 10), L-nitro-L-arginin (NO synthase inhibitor, 10(-4) M; n = 9), D-Lys(3)-GHRP-6 (GHS-R1a antagonist; 10(-4) M; n = 8) or apamin+charybdotoxin (KCa channels blockers; 10(-6) M, n =7 ), as well as after damaging the endocardial endothelium (n = 7). In hypertrophic muscles, ghrelin was added either alone (n = 9) or after pre-treatment with apamin+charybdotoxin (10(-6 M, n=7). Ghrelin concentration-dependently decreased active tension (AT) and maximal velocity of tension rise (negative inotropic effect), as well as, maximal velocity of tension decay (negative lusitropic effect) and time to AT (onset of relaxation). These effects were maximal at 10(-6) M, similar in normal and hypertrophic muscles and were significantly altered only by apamin+charybdotoxin, indomethacin and L-nitro-L-arginin. Apamin+charybdotoxin attenuated the negative inotropic effect, while indomethacin and L-nitro-L-arginin, respectively, blunted and exacerbated the premature onset of relaxation. In conclusion, ghrelin induces negative inotropic and lusitropic effects and an earlier onset of relaxation in normal and hypertrophic myocardium, which are independent of GHS-R1a, since they were not affected by D-Lys(3)-GHRP-6. The negative inotropic effect is partly mediated by KCa channels, while the earlier onset of relaxation is modulated by prostaglandins and NO.
Study Information
pubmed
2006
2006-01-18T00:00:00.000Z
10.1016/j.peptides.2005.12.007
42
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