While acute studies often show apelin counteracting Ang II, the chronic interaction appears more complex; for example, chronic co-administration of apelin-13 failed to prevent Ang II-induced hypertension, cardiac hypertrophy, or fibrosis in rats, a discrepancy that might be explained by the short half-life of apelin-13, receptor desensitization upon continuous stimulation, or the activation of counter-regulatory mechanisms over time [162]. The gene discussed is APLN; the disease is hypertensive disorder.