Cardiac ischemia and impairment of vascular endothelium function in hearts from GH-deficient rats: Protection by hexarelin

Colonna, Vito De Gennaro; Rossoni, Giuseppe; Bernareggi, Micaela; Müller, Eugenio E.; Berti, F.

doi:10.1016/s0014-2999(97)01178-3

Cited by 80 publications

(39 citation statements)

References 31 publications

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“…The cardioprotective effect of hexarelin has also been demonstrated by our group in GH-deficient (De Gennaro-Colonna et al 1997 and in aged rats (Rossoni et al 1998). An interesting finding from our present results is that hexarelin manifested a strong heart protective action with no evidence of stimulation of the somatotropic axis, especially in obese Zucker rats.…”

Section: Discussionmentioning

confidence: 58%

“…This negative finding is also consistent with the inability of hexarelin to alter the vasopressor activity of angiotensin II on the coronary vessels. Overall, these data indicate that in lean and obese Zucker rats, in contrast to rats treated with anti-GHRH serum (De Gennaro-Colonna et al 1997) or hypophysectomized rats , there is neither an evident impairment of the vascular endotheliumdependent relaxing function nor is hexarelin capable of improving the endothelial vasodilation mechanisms. A tentative explanation of these results is that a clear dysfunction of the endothelium-dependent relaxing mechanisms is present only when the somatotropic function is lacking or is profoundly impaired, such as in hypophysectomized or anti-GHRH-treated rats respectively, but not when the GH secretion is decreased to a lesser extent, such as in obese Zucker rats.…”

Section: Discussionmentioning

confidence: 75%

“…These findings are in agreement with recent results obtained by our group in beagle dogs treated with hexarelin for 16 weeks (A Rigamonti, unpublished data) and, to the best of our knowledge, they represent the first demonstration that hexarelin has a cholesterollowering effect. It is tempting to suggest that this effect might contribute to the cardioprotective activity displayed by the peptide in rats (De Gennaro-Colonna et al 1997). In this study, we have not evaluated the plasma levels of low density lipoprotein (LDL)/high density lipoprotein (HDL) cholesterol, but our finding of decreased cholesterol levels in hexarelin-treated obese rats could be due to a decrease in LDL cholesterol with minor changes in HDL cholesterol.…”

Section: Discussionmentioning

confidence: 88%

“…Lean and obese Zucker rats were assigned to 4 experimental groups, as follows: 1) lean rats treated with saline (1 ml/kg, s.c.) (LEAN+SAL); 2) lean rats treated with hexarelin (80 µg/kg, b.i.d., s.c.) (LEAN+HEXA); 3) obese rats treated with saline (1 ml/kg, s.c.) (OBESE+SAL); 4) obese rats treated with hexarelin (80 µg/kg, b.i.d., s.c.) (OBESE+HEXA). The length of treatment with hexarelin or saline was 30 days, somewhat longer than that previously used in rats with selective GH deficiency (15 days) (De Gennaro-Colonna et al 1997). The complexity of the experimental model used in this study, i.e.…”

Section: Animals and Treatmentsmentioning

confidence: 91%

“…Based on these findings, we thought it would be of interest to evaluate whether, in male obese Zucker rats, chronic treatment with hexarelin, a synthetic enkephalinderived hexapeptide with a potent GH-releasing activity (Deghenghi et al 1994), might be able to ameliorate the somatotropic function and reverse some metabolic alterations associated with obesity. Furthermore, as decreased GH secretion and insulin resistance (Modan et al 1985) are associated with increased cardiovascular risk, and hexarelin proved able to exert protective cardiovascular effects in GH-deficient rats and old rats (De Gennaro-Colonna et al 1997, Rossoni et al 1998, we also tested the capacity of this hexapeptide to prevent postischemic ventricular dysfunction in the hearts of male obese Zucker rats. For comparison, treatment with hexarelin and evaluation of all biochemical and cardiovascular parameters were also performed in a group of male lean Zucker rats.…”

Section: Introductionmentioning

confidence: 99%

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Endocrine, metabolic and cardioprotective effects of hexarelin in obese Zucker rats

Gennaro-Colonna

Rossoni²,

Cocchi³

et al. 2000

Journal of Endocrinology

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Genetically obese male Zucker rats have an impaired secretion of GH, coupled to hyperinsulinemia, hyperlipidemia and glucose intolerance. The aim of this study was to evaluate whether a chronic treatment with hexarelin, a synthetic enkephalin-derived hexapeptide with a potent GH-releasing activity, might be able to ameliorate the somatotropic function and reverse some metabolic alterations associated with obesity in male obese Zucker rats. Furthermore, as decreased GH secretion and insulin resistance are associated with increased cardiovascular risk, we also tested the capacity of hexarelin to prevent postischemic ventricular dysfunction in hearts of male obese Zucker rats. Obese and lean male rats of the Zucker strain were treated with hexarelin (80 µg/kg, b.i.d., s.c.) or saline (1 ml/kg, b.i.d., s.c.) for 30 days. An acute hexarelin injection (80 µg, s.c.) at the 28th day of treatment elicited a rise in plasma GH levels in lean but not in obese rats (pretreated or not with hexarelin); lean rats chronically treated with hexarelin showed a greater increase in plasma GH as compared with control counterparts. At the end of the experiment, pituitary GH mRNA levels were significantly reduced in obese rats and hexarelin administration failed to increase pituitary GH mRNA and IGF-I concentrations in plasma and heart. Chronic treatment with hexarelin increased insulinemia and blood glucose levels in obese but not in lean rats, left unaltered the high triglyceride levels but significantly decreased plasma cholesterol concentrations in obese rats. Heart preparations from lean and obese Zucker rats treated with saline, subjected to low flow ischemia and reperfusion, showed at reperfusion: a) a low recovery of postischemic left ventricular developed pressure (LVDP), coupled to a substantial increase in coronary perfusion pressure, and b) a marked increase in creatine kinase released in the perfusates. Hexarelin administration for 30 days counteracted the heart ischemic damage both in lean and obese Zucker rats. In fact, the recovery of LVDP at reperfusion was significantly higher than in controls and the increase in coronary resistance was minimal. Collectively, these data indicate that a 30-day treatment with hexarelin was unable to improve somatotropic function in male obese Zucker rats but was successful in decreasing plasma cholesterol concentrations. Hexarelin exerted a cardioprotective effect in both lean and obese rats. The heart-protective activity afforded by the peptide was divorced from any stimulation of the GH axis and is probably exerted through activation of specific cardiac receptors.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 88%

Section: Animals and Treatmentsmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Endocrine, metabolic and cardioprotective effects of hexarelin in obese Zucker rats

Gennaro-Colonna

Rossoni²,

Cocchi³

et al. 2000

Journal of Endocrinology

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Hexarelin, a growth hormone secretagogue, protects the isolated rat heart from ventricular dysfunction produced by exposure to calcium-free medium

Rossoni

Locatelli

Colonna

et al. 2000

Pharmacological Research

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Hormones Signaling and Myocardial Ischemia

Pantos¹,

Cokkinos

2006

Myocardial Ischemia

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Although hormones constitute an important component of the adaptive response of the hving organism to various stresses, their role in myocardial ischemia has not been adequately explored. However, recent research reveals that hormone signaling is of physiological relevance in the context of ischemia and reperfusion. Furthermore, hormones or hormones' analogs are suggested as potential therapeutic agents for treating heart diseases. ESTROGENSClinical observations have suggested a cardioprotective role for estrogens. Consistent with this notion are several experimental reports. Acute administration of 17p-estradiol before ischemia and at reperfusion is shown to increase functional recovery and reduce lactate dehydrogenase (LDH) release in perfused rat hearts from ovariectomized rats. This effect was associated with less intracellular Na"" and Ca^^ and a blunted reduction in pH^ Similarly, acute pre-ischemic administration of 17p-estradiol and not 17a-estradiol limited infarct size in an in vivo model of coronary artery occlusion and reperfusion in ovariectomized rabbits. This response was abrogated by the administration of ICI 182,780, an estrogen receptor antagonist^ However, in a canine model of coronary occlusion and reperfusion, although 17p-estradiol reduced infarct size and arrhythmias, the administration of ICI 182,780 did not abolish these effects. Pretreatment with 5-hydroxydecanoate, a mitochondrial K^^ channel blocker abrogated the estrogen infarct size limiting effect while blockade of sarcolemmal K^^ channel abolished the effect of estrogen on reperfusion ventricular arrhythmias^. In open-chest dogs, infarct size and reperfusion ventricular arrhythmias were reduced by estrogen administration and this response was abrogated by inhibition of the NO synthase (NOS) or calcium-

show abstract

Cardiac ischemia and impairment of vascular endothelium function in hearts from GH-deficient rats: Protection by hexarelin

Cited by 80 publications

References 31 publications

Endocrine, metabolic and cardioprotective effects of hexarelin in obese Zucker rats

Endocrine, metabolic and cardioprotective effects of hexarelin in obese Zucker rats

Hexarelin, a growth hormone secretagogue, protects the isolated rat heart from ventricular dysfunction produced by exposure to calcium-free medium

Hormones Signaling and Myocardial Ischemia

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