Chronic Administration of Ghrelin Improves Left Ventricular Dysfunction and Attenuates Development of Cardiac Cachexia in Rats With Heart Failure

Abstract

Background-Ghrelin is a novel growth hormone (GH)-releasing peptide that may also induce vasodilation and stimulate feeding through GH-independent mechanisms. We investigated whether ghrelin improves left ventricular (LV) dysfunction and attenuates cardiac cachexia in rats with chronic heart failure (CHF). Methods and Results-Ligation of the left coronary artery or sham operation was performed; 4 weeks after surgery, rat ghrelin (100 g/kg SC BID) or saline was administered for 3 weeks. Echocardiography and cardiac catheterization were performed. Serum GH and insulin-like growth factor-1 were significantly higher in both CHF and sham rats treated with ghrelin than in those given placebo (PϽ0.05 for both). CHF rats given placebo showed an impaired increase in body weight compared with sham rats given placebo (PϽ0.05). CHF rats treated with ghrelin, however, showed a significantly greater increase in body weight than those given placebo (ϩ10% versus ϩ3%, PϽ0.05). They showed significantly higher cardiac output (315Ϯ49 versus 266Ϯ31 mL · min Ϫ1 · kg Ϫ1 , PϽ0.05) and LV dP/dt max (5738Ϯ908 versus 4363Ϯ973 mm Hg/s, PϽ0.05) than CHF rats given placebo. Ghrelin increased diastolic thickness of the noninfarcted posterior wall, inhibited LV enlargement, and increased LV fractional shortening in CHF rats (from 15Ϯ3% to 19Ϯ3%, PϽ0.05). Conclusions-Chronic subcutaneous administration of ghrelin improved LV dysfunction and attenuated the development of LV remodeling and cardiac cachexia in rats with CHF.

Endogenous production of ghrelin and beneficial effects of its exogenous administration in monocrotaline-induced pulmonary hypertension

“…Decreased RV overload will primarily favor recovery of RV function and structure. With regard to the LV, previous studies also showed that chronic administration of Ghr was able to improve LV dysfunction and to attenuate the development of LV remodeling and cardiac cachexia in rats with heart failure (23).…”

“…Ghr administration reduces cardiac afterload and increases cardiac output without increasing heart rate in both normal subjects and patients with dilated cardiomyopathy (20,21). In addition, Ghr has potent vasodilator properties that are endothelium and GH independent (23,37). The Ghr-GHSR signaling pathway is, therefore, presumably involved in the regulation of vascular tone (21,37).…”

Effect of Food Restriction on Ghrelin in Normal‐Cycling Female Rats and in Pregnancy

“…Ghrelin seems to play an important role in GH secretion, energy balance (21), and body-weight homeostasis, as well as cardiac and hemodynamic functions (22). Undernutrition at different stages of life can lead to persistent abnormalities in growth and cardiovascular function.…”

Blood biomarkers of insulin resistance in acute stroke patients treated with intravenous thrombolysis: Temporal profile and prognostic value

“…Animal models of permanent focal cerebral ischemia in rats showed that ghrelin treatment results in decreased infarct size and neurological deficit through suppression of inflammation, nNOS activity, and apoptosis [34]. In both animal [35] and human [36] studies of cardiac disease, ghrelin improved left ventricular structure and function, exercise capacity and muscle wasting, suggesting that ghrelin could be a new therapeutic approach for the treatment of cardiac heart failure. The role of leptin and ghrelin in human cerebral ischemia needs to be further clarified.…”