Biomedical subjects

A Torsello

Publications and source records attributed to A Torsello.

At least 19 recordsLinked to original sources

PubMed2006

TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity.

The vgf gene has been identified as an energy homeostasis regulator. Vgf encodes a 617-aa precursor protein that is processed to yield an incompletely characterized panel of neuropeptides. Until now, it was an unproved assumption that VGF-derived peptides could regulate metabolism. Here, a VGF peptide designated TLQP-21 was identified in rat brain extracts by means of immunoprecipitation, microcapillary liquid chromatography-tandem MS, and database searching algorithms. Chronic intracerebroventricular (i.c.v.) injection of TLQP-21 (15 mug/day for 14 days) increased resting energy expenditure (EE) and rectal temperature in mice. These effects were paralleled by increased epinephrine and up-regulation of brown adipose tissue beta2-AR (beta2 adrenergic receptor) and white adipose tissue (WAT) PPAR-delta (peroxisome proliferator-activated receptor delta), beta3-AR, and UCP1 (uncoupling protein 1) mRNAs and were independent of locomotor activity and thyroid hormones. Hypothalamic gene expression of orexigenic and anorexigenic neuropeptides was unchanged. Furthermore, in mice that were fed a high-fat diet for 14 days, TLQP-21 prevented the increase in body and WAT weight as well as hormonal changes that are associated with a high-fat regimen. Biochemical and molecular analyses suggest that TLQP-21 exerts its effects by stimulating autonomic activation of adrenal medulla and adipose tissues. In conclusion, we present here the identification in the CNS of a previously uncharacterized VGF-derived peptide and prove that its chronic i.c.v. infusion effected an increase in EE and limited the early phase of diet-induced obesity.

Adipose Tissue, Brown↗

PubMed2006

Vascular endothelial growth factor (VEGF) expression in noise-induced hearing loss.

Noise-induced hearing loss has been associated with alterations in cochlear blood flow. Our study analyzed the expression of Vascular Endothelial Growth Factor (VEGF) and its functional receptors, Flt-1 and Flk-1, in the cochlear structures of noise-exposed and unexposed guinea pigs. VEGF is a prototypical angiogenic agent, with multiple functions on vascular biology, ranging from vascular permeability to endothelial cell migration, proliferation, differentiation, and survival. Acoustic trauma was induced by a continuous pure tone of 6 kHz, at 120 dB SPL for 30 min. Auditory function was evaluated by electrocochleographic recordings at 2-20 kHz for 7 days. Noise-induced cochlear morphological changes were studied by immunohistochemistry and scanning electron microscopy. The expression of VEGF and its receptors was examined by immunohistochemistry and western blotting analysis. The hearing threshold shift reached a level of 60 dB SPL on day 1 after trauma and underwent a partial recovery over time, reaching a value of about 20 dB SPL on day 7. Outer hair cell loss was more prominent in the area located 14-16 mm from the apex. Increased cochlear VEGF expression was observed in noise-exposed animals, in particular at the level of stria vascularis, spiral ligament, and spiral ganglion cells. No changes were observed in the expression of VEGF-receptors. Our data suggest a role for VEGF in the regulation of the vascular network in the inner ear after acoustic trauma and during auditory recovery, with potentially important clinical and therapeutic implications.

Action Potentials↗

PubMed2006

Obestatin inhibits feeding but does not modulate GH and corticosterone secretion in the rat.

Obestatin is a recently discovered 23 amino acids peptide derived from the ghrelin gene. As opposed to ghrelin, obestatin was shown to inhibit food intake in mice. The aims of this research were to study the effects of acute obestatin treatment on feeding behavior in the rat and its effects on GH and corticosterone secretion. Our results demonstrate that in young-adult male rats, obestatin effectively blunts the hunger caused by short-term starvation. Obestatin did not modify GH secretion in 10-day-old rats and did not antagonize the GH-releasing effects of hexarelin. Moreover, obestatin administration had no effects on spontaneous corticosterone secretion. In conclusion, these data demonstrate that in young-adult male rats the newly discovered obestatin can inhibit feeding but does not modify GH and corticosterone release in infant rats.

Animals↗

PubMed2005

Ghrelin in gastroenteric pathophysiology.

Ghrelin, an acylated peptide produced predominantly by the stomach, has been discovered to be a natural ligand of the growth hormone secretagogue receptor 1a (GHS-R1a). It is localized in distinct cells of the gastric mucosa, mainly distributed in the mid portion of the oxyntic gland characterized by P/D1 granules in man and X/A-like granules in rodents. The ghrelin cell represents the second most frequent endocrine cell type after the enterochromaffin-like cells in gastric oxyntic mucosa, pointing to a potentially relevant role in the physiology of the stomach. Ghrelin has no relevant homology with any known gastrointestinal peptide and displays strong GH-releasing activity both in animals and in humans. However, in addition to stimulating GH secretion, ghrelin possesses several other endocrine and extraendocrine biological activities that are explained by the widespread distribution of ghrelin and GHS-R1a expression. In the rat, ghrelin exerts a control in gastric acid secretion and motility: the gastric acid secretion is stimulated by peripheral administration of high doses of ghrelin, but inhibited by very low doses of ghrelin delivered into the central nervous system. Moreover, ghrelin provides a potent and dose-related gastroprotective action against ethanol- and stress-induced gastric ulcers. The integrity of both nitric oxide (NO) system and capsaicin afferent nerves are required for the gastroprotective effect of ghrelin, whereas the vagus nerve might be involved in conveying ghrelinergic signal from periphery to the brain. In addition, prostaglandins derived by the constitutive cyclooxygenase (COX) activity are essential for the protective activity of ghrelin in ethanol and stress-induced gastric lesions. Given its prevailing role in physiological and pathophysiological gastric function, the discovery of ghrelin will open new perspectives and potential clinical implications in the gastroenteric field.

Animals↗

PubMed2005

GH-releasing peptides and bone.

It has been extensively demonstrated that GH secretagogues (GHS) play a role in the regulation of bone metabolism in animals and humans. Unlike GH, administration of GHS does not increase bone resorption markers, suggesting that a mechanism exclusively linked to GH release cannot account for the effect of these compounds. On this line, we investigated the effect of GHS and ghrelin, the endogenous ligand of GHS receptors, on bone cells. We found that both hexarelin and ghrelin significantly stimulated cell proliferation and increased alkaline phosphatase and osteocalcin production in primary cultures of rat calvaria osteoblasts. In the same cells, we were able to detect the mRNA for the GHS receptor by RT-PCR and the corresponding protein by Western blot, indicating that ghrelin and GHS may bind and activate this receptor. Two isoforms of GHS receptors (GHS-R), which are presumably the result of alternate processing of pre-mRNA, have been identified and designed receptors 1a (R1a) and 1b (R1b). Ghrelin, the endogenous ligand of the GHS receptors, binds with high affinity GHS-R1a only. Unlike fetal calvaria cells, osteoblasts derived from adult rat tibia did not express the GHS-R1 a, but only the biologically inactive isoform GHS-R1b. The latter isoform was present in only one of the three specimens of human osteoblasts obtained from the iliac crest or the upper femur of patients during surgery. These results would indicate that only osteoblasts from fetal bone express functional receptors responsive to ghrelin and GHS.

Animals↗

PubMed2004

IGF-I stimulates proliferation of spontaneously immortalized human keratinocytes (HACAT) by autocrine/paracrine mechanisms.

HaCaT keratinocytes are derived from adult human skin and although spontaneously immortalized, remain highly related to their normal counterparts. We observed that HaCaT cells can proliferate in serum-free medium (SFM), in contrast to normal human keratinocytes whose growth in vitro requires a feeder layer and/or the supplementation with hormones and growth factors. Since autocrine production of growth factors has been proposed as the pathway that cells may exploit to escape growth regulation, we have investigated whether this is occurring in HaCaT cultured in SFM. Either epidermal growth factor (EGF) or insulin-like growth factor-1 (IGF-I) was effective and dose-dependently stimulated HaCaT replication. The ability of these keratinocytes to express EGF and IGF-I and their receptors was investigated by northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR). We report that HaCaT cells synthesize mRNAs for IGF-I, IGF-II, IGF-IR and EGF-R but not EGF mRNA. Immunoneutralization of IGF-I with specific monoclonal antibodies blocked spontaneous HaCaT proliferation in SFM, as did incubation with antibodies against IGF-IR. These data demonstrate that an autocrine/paracrine loop based on IGF-I may allow HaCaT keratinocytes to proliferate autonomously in culture in contrast to keratinocytes in primary culture. A similar mechanism may be involved in the development of hyperproliferative diseases of human skin and its functional disruption may represent the target for therapeutic approaches.

Adult↗

PubMed2004

Effects of hexarelin against acid-independent and acid-dependent ulcerogens in the rat.

The effects of intracerebroventricular (icv) or subcutaneous (sc) hexarelin (Hexa) administration, against gastric ulcers induced by ethanol (50%, 1 ml/rat/os) or Indomethacin (20 mg/kg/os) were examined in conscious rats. Hexa at 1 nmol/rat, icv or 10 nmol/kg, sc reduced ethanol-induced ulcers by 47% and 32% respectively. Hexa, but not ghrelin significantly worsened (+40%) Indomethacin-induced ulcers when injected sc. Hexa-gastroprotection against ethanol-induced ulcers was removed by the GHS-R antagonist (D-Lys3)-GRPR-6 and by the inhibitor of NO-synthase (NOS) Nomega-nitro-L-arginine methyl ester. Semiquantitative RT-PCR assay of gastric NOS mRNA isoforms revealed that the reduction in iNOS-derived NO and the increase of constitutive-derived NO are relevant for the gastroprotection of Hexa against ethanol-induced gastric damage.

Animals↗

PubMed2004

Modifications of plasma concentrations of hormonal and tissue factors during mechanical ventilation with positive end-expiratory pressure.

AIM: The aim of this study is to analyse if the decrease of cardiac performance due to positive end-expiratory pressure (PEEP) application, within low values applied in clinical practice (5 cm H(2)O) is able to trigger a response of the main endogenous factors which control and maintain the mean arterial pressure (MAP). METHODS: This study was applied to 18 patients, admitted to the Intensive Care Unit (ICU) of the University Hospital of Modena, who underwent oro-tracheal intubation and mechanical ventilation. On admission, patients did not suffer from cardiac or lung disease. This study analyses plasma concentrations of epinephrine, norepinephrine, ET-1, NO metabolites, renin, aldosterone at 4 different times: before PEEP application, 60 minutes after the beginning of mechanical ventilation with PEEP, and respectively 30 and 60 minutes after withdrawal of PEEP. At the same time, MAP values and heart rate (HR) have been observed. RESULTS: Results show an increase of epinephrine and norepinephrine after PEEP application and a decrease to basal values at PEEP withdrawal. All variations are statistically significant. After PEEP introduction, ET-1 showed an increased concentration, although it was not statistically significant, while a significant decreasing trend was observed after PEEP withdrawal. A significant increase of NO metabolite values has been observed together with the increase of ET-1, followed by a decrease to basal values after the withdrawal of PEEP. Concentrations of renin increased when PEEP was applied even though they were not significant and decreased significantly when PEEP was withdrawn. A similar trend was revealed by aldosterone even though it underwent constant significant variations. CONCLUSION: The administration of PEEP produces an effective response of endogenous substances whose function is to maintain a proper tissue perfusion.

Adult↗

PubMed2003

Moexipril and quinapril inhibition of tissue angiotensin-converting enzyme activity in the rat: evidence for direct effects in heart, lung and kidney and stimulation of prostacyclin generation.

The activation of angiotensin converting enzyme (ACE) may contribute to the development of vascular and myocardial structural changes. The level of ACE is stable in human plasma, and only limited data are available on its regulation at the tissue level. The aim of this study was to characterize the effects of two ACE inhibitors, moexipril and quinapril on tissue ACE activity. Adult male rats were treated intragastrically once daily for 6 days either with 2 mg/kg moexipril or quinapril. After single treatment, moexipril and quinapril effectively inhibited ACE activity in plasma and slightly in heart and aorta, whereas after 6 days of treatment they inhibited ACE activity in plasma (87% and 94%, respectively), lung (92% and 93%), myocardium (26% and 23%), kidney (21% and 20%), and aorta (39% and 40%), but not in skeletal muscle. Interestingly, the two ACE-inhibitors also induced a significant increase in cardiac homogenates of 6-keto-PGF1alpha levels, an important index of PGI2 generation. To test whether the reduced effects of ACE inhibitors in heart and kidney were caused by a limited availability of the drugs, 100 microl of lung, heart and kidney homogenates from control rats were incubated in vitro with moexipril and quinapril immediately before assay. Both drugs were more effective in lung than heart and kidney homogenates, with inhibition values superimposable to those obtained in vivo. These results clearly indicate that inhibition of tissue ACE activity does not depend primarily on the availability of ACE inhibitors in each organ.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

Ghrelin protects against ethanol-induced gastric ulcers in rats: studies on the mechanisms of action.

Ghrelin, the endogenous ligand for GH secretagogue receptors, has been reported to influence acid gastric secretion and motility, but its potential gastroprotective effect is unknown. The aims of this study were 1) to examine the effects of central and peripheral administration of ghrelin on ethanol-induced gastric ulcers in conscious rats, and 2) to investigate the possible roles of nitric oxide (NO), vagal nerve, and sensory fibers in the gastric effects of ghrelin. Ghrelin was administered either intracerebroventricularly or sc 30 min before ethanol, and mucosal lesions were examined macroscopically. Additionally, rats were either treated with the inhibitor of NO synthesis N(omega)-nitro-L-arginine methyl ester (L-NAME) or underwent bilateral cervical vagotomy or capsaicin-induced sensory denervation. Conventional histology and immunohistochemistry for ghrelin, gastrin, and somatostatin were performed on gastric specimens from representative rats. Central ghrelin (4-4,000 ng/rat) dose-dependently reduced ethanol-induced gastric ulcers by 39-77%. Subcutaneous ghrelin administration (80 micro g/kg) reduced ulcer depth only. L-NAME and capsaicin, but not vagotomy, prevented the gastroprotective effect of central ghrelin (4000 ng/rat). This is the first evidence that ghrelin exerts a potent central gastroprotective activity against ethanol-induced lesions. The gastroprotective effect of ghrelin is mediated by endogenous NO release and requires the integrity of sensory nerve fibers.

Animals↗

PubMed2002

EP1572: a novel peptido-mimetic GH secretagogue with potent and selective GH-releasing activity in man.

EP1572 UMV1843 [Aib-DTrp-DgTrp-CHO]) is a new peptido-mimetic GH secretagogue (GHS) showing binding potency to the GHS-receptor in animal and human tissues similar to that of ghrelin and peptidyl GHS. EP1572 induces marked GH increase after s.c. administration in neonatal rats. Preliminary data in 2 normal young men show that: 1) acute i.v. EP1572 administration (1.0 microg/kg) induces strong and selective increase of GH levels; 2) single oral EP1572 administration strongly and reproducibly increases GH levels even after a dose as low as 0.06 mg/kg. Thus, EP1572 is a new peptido-mimetic GHS with potent and selective GH-releasing activity.

Adult↗

PubMed2002

Evidence for a central inhibitory role of growth hormone secretagogues and ghrelin on gastric acid secretion in conscious rats.

We examined the possible central and peripheral effects of synthetic growth hormone secretagogues (GHS), hexarelin (Hexa) and EP 40737 (D-Thr-D-Trp (2-Me)-Ala- Trp-D-Phe-Lys-NH2), and of their endogenous counterpart, ghrelin, on gastric acid secretion. The compounds were administered intracerebroventricularly (i.c.v.) or subcutaneously (s.c.) in conscious male rats and the volume of gastric secretion and gastric acid output were examined 3 h after pylorus ligation (Shay-test). Central Hexa, EP 40737 and ghrelin administration (from 0.1 pmol to 1 nmol/rat, i.c.v.) significantly inhibited gastric acid secretion. The maximum inhibitory effect on gastric acid output was detected at the dose of 10 pmol/rat, i.c.v. for Hexa (-51.3%), of 100 pmol/rat, i.c.v. for EP 40737 (-70%) and of 1 pmol/rat, i.c.v. for ghrelin (-60%). All peptides were less effective at the highest dose used (1 nmol/rat, i.c.v.). Hexa, EP 40737 and ghrelin injected s.c. did not modify gastric acid secretion. The inhibitory action of Hexa on gastric acid secretion seems to involve brain somatostatinergic system since Hexa (10 pmol/rat, i.c.v.) did not inhibit gastric acid secretion in rats pretreated (4 h before) with cysteamine (300 mg/kg, s.c.), a depletor of endogenous somatostatin. These results show that synthetic GHS and ghrelin exert a central long-lasting inhibitory effect on gastric acid secretion in conscious pylorus-ligated rats. The fact that very low doses of ghrelin and GHS inhibit gastric secretion, provide evidence for a tonic inhibitory role of the peptides in the central control of gastric secretory function.

Animals↗

PubMed2002

[Ghrelin and GH secretion].

Ghrelin is an acylated peptide recently isolated from rat and human stomach that potently stimulates GH release in vivo and in vitro in rats and humans. Ghrelin specifically activates the receptor for the growth hormone secretagogues (GHS) and it has been proposed that it may be the endogenous ligand mimicked by these synthetic compounds. Ghrelin is primarily produced in endocrine cells of the stomach, and to a lesser extent, in other peripheral tissues, including the pituitary. Although ghrelin is the most potent GH-secretagogue so far identified, its circulating levels do not correlate with those of GH either in physiological and pathological conditions. Because of these and many other observations, it may be postulated that ghrelin is not physiologically involved in the regulation of growth hormone secretion. Nonetheless, ghrelin may serve as a very useful model for the development of more potent synthetic GHS, which may be therapeutically useful for the treatment of human GH deficiency.

Amino Acid Sequence↗

PubMed2001

Isolation of normal epithelial cells adapted to grow at nonphysiological concentration of magnesium.

Extracellular magnesium (Mg) depletion inhibits the growth of the HC11 normal mammary epithelial cells. In this study we found that an acute increase in extracellular Mg generally exerts a positive effect on the growth of these cells. We also isolated and characterized two derivatives adapted to grow and proliferate at nonphysiological concentration of Mg. The growth properties of the HC-LMg cells at 25 microM Mg were comparable to those of the parental HC11 cells in the regular medium (0.5 mM Mg) despite an increased expression of the CDK inhibitor p27(Kip1). They also showed a reduced dependence from serum to grow. The HC-HMg cells have been adapted to grow and proliferate at an increased (45 mM) Mg concentration. Cell total Mg content was 19.6, 9.7, and 20.1 nmol/mg protein in the HC11, HC-LMg, and HC-HMg cells, respectively. Thus, we have isolated derivatives of normal epithelial cells which are able to maintain Mg content in a physiological range in the face of different extracellular concentration gradients and will be a valuable tool for further studies on the regulation of Mg homeostasis in eukaryotic cells.

Animals↗

PubMed2001

Penile erection induced by EP 80661 and other hexarelin peptide analogues: involvement of paraventricular nitric oxide.

The effect of GAB-D-Trp(2-Me)-D-Trp(2-Me)-LysNH(2) (EP 80661), GAB-D-Trp(2-Me)-D-Trp(2-Me)-D-Trp(2-Me)-LysNH(2) (EP 60761), GAB-D-Trp(2-Me)-LysNH(2) (EP 91071) and GAB-D-Trp(2-Me)-D-beta Nal-Phe-LysNH(2) (EP 50885), four hexarelin peptide analogues that induce penile erection when injected into the paraventricular nucleus of the hypothalamus of male rats, on the concentration of NO(2)(-) and NO(3)(-) in the paraventricular dialysate was studied in male rats. EP peptides (1 microg) induced penile erection and increased the concentration of NO(2)(-) and NO(3)(-) in the paraventricular dialysate. In contrast, hexarelin (1 microg) was ineffective on either penile erection or paraventricular NO(2)(-) and NO(3)(-). EP peptide-induced penile erection was prevented by the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methylester given into the paraventricular nucleus (20 microg), which also reduced the concomitant increase of NO(2)(-) and NO(3)(-) concentration in the paraventricular dialysate. In contrast, the oxytocin receptor antagonist [d(CH(2))(5)Tyr(Me)(2)-Orn(8)]vasotocin (1 microg) given into the paraventricular nucleus, was ineffective on penile erection and on the NO(2)(-) and NO(3)(-) increase induced by EP peptides, despite its ability to prevent the sexual response induced by the above peptides when given into the lateral ventricles. The present results show that EP peptides induce penile erection by activating nitric oxide synthase in the paraventricular nucleus of the hypothalamus, possibly in the cell bodies of oxytocinergic neurons that control penile erection.

Animals↗

PubMed2001

Growth hormone-inhibiting activity of cortistatin in the rat.

Cortistatin-14 (CST-14) is an endogenous neuropeptide with notable structural similarities to native somatostatin-14 (SS-14), but different physiological functions. Differences in the physiology of the two peptides do not provide conclusive evidence for a specific receptor for CST. To date, the effects of CST-14 on anterior pituitary hormones have never been reported. Aim of this study was to investigate the in vivo effects of CST-14 on GH secretion in comparison to SS-14. Our results demonstrate that CST-14 was very effective in reducing GH secretion in normal male anaesthetized rats. Its activity was similar to that of SS-14 and had a rapid onset and a slightly longer duration of action. In conclusion, we have reported for the first time that CST is a potent and effective inhibitor of GH release in rats and that its action may be mediated by the interaction with one or different SS receptor subtypes.

Animals↗

PubMed2001

DNA oxidative damage during differentiation of HL-60 human promyelocytic leukemia cells.

DNA oxidative damage was measured in human promyelocytic leukemia HL-60 cells, in the same cells committed to granulocytic differentiation with dimethyl sulfoxide (DMSO) or all-trans-retinoic acid (RA) and in mature human peripheral granulocytes (HPG). DNA damage was evaluated as single strand breaks and 8-OHdG adducts, measured by single cell electrophoresis or by monoclonal antibodies, respectively. The basal levels of either marker of DNA damage were higher in undifferentiated HL-60 cells than in HPG and DMSO- or RA-differentiated cells. Treatment with H(2)O(2) increased 8-OHdG formation in all cells, but the levels of DNA damage remained higher in undifferentiated cells as compared to the differentiated ones. Three lines of evidence suggested that the higher levels of DNA damage observed in undifferentiated cells were at least in part attributable to a reduced detoxification of reactive oxygen species (ROS). First, undifferentiated cells were shown to accumulate higher levels of dichlorodihydrofluorescein-detectable ROS than HPG and DMSO- or RA-differentiated cells. Second, undifferentiated HL-60 cells were characterized by reduced levels of GSH and lower GSH/GSSG ratios as compared to the differentiated cells. Third, pretreatment of undifferentiated HL-60 cells with antioxidants such as alpha-tocopherol or beta-carotene suppressed the elevation of ROS and the formation of 8-OHdG induced by H(2)O(2). Further evidence for the importance of the oxidant/antioxidant balance was obtained by modulating the iron-catalyzed decomposition of H(2)O(2) to hydroxyl radicals in undifferentiated HL-60 cells. In fact, pretreatment with FeSO(4) increased the formation of 8-OHdG induced by H(2)O(2), whereas pretreatment with the iron chelator deferoxamine produced the opposite effect. These results illustrate correlations between the oxidant/antioxidant balance and DNA damage and suggest that the capability of a cell population to withstand oxidative stress and DNA damage may depend on its degree of differentiation.

Antibodies, Monoclonal↗

PubMed2001

Hexarelin, but not growth hormone, protects heart from damage induced in vitro by calcium deprivation replenishment.

The effects of hexarelin, a growth hormone (GH) secretagogue, and human GH on the mechanical and metabolic changes measured in isolated rat hearts submitted to 5 min of Ca2+ deprivation followed by reperfusion with Ca2+-containing medium, the so-called calcium paradox phenomenon, were studied. Hexarelin (80 microg/kg bid, subcutaneously) administered for 7 d to male rats effectively antagonized the sudden increase in resting tension measured in vitro on Ca2+ repletion. Moreover, during Ca2+ repletion the release of creatine kinase activity (an index of cell damage) in the perfusate of these hearts was reduced up to 40% compared with controls. By contrast, administration of hexarelin for 3 d or GH (400 microg/kg bid, subcutaneously) for 7 d did not affect the mechanical and metabolic alterations induced by the calcium paradox. To assess its direct and acute cardiac effects, hexarelin (8 microg/mL) was perfused in vitro in recirculating conditions for 60 min through the hearts of normal rats. In this case, hexarelin did not stimulate heart contractility and failed to prevent ventricular contracture upon Ca2+ readmission, whereas diltiazem, a Ca2+channel blocker, effectively antagonized the calcium paradox phenomenon. We conclude that short-term in vivo exposure to hexarelin, but not GH, enables cardiac myocyites to prevent cytoplasmatic electrolytic unbalance and to control intracellular Ca2+ gain, two functions largely impaired during the calcium paradox phenomenon. Moreover, because the effect of hexarelin is not acute but dependent on the length of in vivo treatment, we suggest that it requires modifications of myocardiocyte physiology.

Animals↗