Positive inotropic effect of somatostatin in guinea-pig ventricular muscles

Hirai, Shozo; Hasegawa, Junichi; Mashiba, Hiroto

doi:10.1016/0022-2828(89)90826-2

Cited by 10 publications

(5 citation statements)

References 32 publications

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“…This hypothesis is consistent with the experimental data demonstrating somatostatin receptors in cardiomyocytes [43] as well as in human myocardic tissue [44]. Moreover, experimental data in the literature would suggest that somatostatin and its analogs may affect the neurotransmission in the central nervous system with consequent possible effects on heart rate and ventricular contractility [45][46][47][48], as well as the rennin-angiotensin-aldosteron system with consequent modification of pre-load and post-load [49]. Moreover, somatostatin and its analogues have also been reported to inhibit cardiomyocyte proliferation via negative modulation of tissue IGF-I expression and to inhibit smooth muscle cell and cardiomyocyte proliferation as well as atherosclerotic degeneration and mechanisms leading to heart transplant rejection [50].…”

Section: Discussionsupporting

confidence: 81%

The long-term cardiovascular outcome of different GH-lowering treatments in acromegaly

et al. 2007

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The aim of this longitudinal study was to evaluate the echocardiographic outcome of acromegalic heart disease in patients undergoing different therapeutic approaches, in order to investigate whether SSA could provide therapeutic advantages as compared with neurosurgery. In total of 36, consecutive patients undergoing SSA treatment after neurosurgery were enrolled in this study (Gr.Surg.-SSA). After 12 months of treatment, 21 patients had a controlled disease, while the remaining 15 patients displayed uncontrolled disease. Twelve acromegalic patients who did not undergo SSA treatment due to controlled disease after neurosurgery were enrolled as control group (Gr.Surg). The echocardiographic-Doppler study was performed before neurosurgery and after 12-months of follow-up. After follow-up, a significant reduction in serum GH and IGF-I values, Left Ventricular Mass index (LVMi) and LVH rate with an improvement in diastolic function was observed in both groups of patients. We found a significant reduction of LVMi either in patients with controlled disease or in those with poorly controlled disease undergoing SSA treatment. Diastolic function and of LVH percentage improved in all groups, but significantly so only in controlled patients, no significant difference in any echocardiographic parameters and in the prevalence of the LVH rate were observed between the three groups of patients at the end of follow-up. Therefore, our data appear to show that for echographic parameters medical treatment additive beneficial effects is compared to neurosurgery alone. SSA also appears to contribute to the improvement of acromegalic cardiomyopathy also in patients who did not achieve biochemical control of the disease.

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Section: Discussionsupporting

confidence: 81%

The long-term cardiovascular outcome of different GH-lowering treatments in acromegaly

et al. 2007

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“…However, accumulation of localized hormone may have a negative regulatory role. Previous studies showed that somatostatin inhibits myocyte contraction in atrium while eliciting a positive response in ventricular muscles possibly due to an increase in the slow inward Ca 2ϩ current (13). Nonetheless, data from our Langendorff apparatus study revealed that neuronostatin perfusion suppressed LVDP, ϮdL/dt and heart rate, favoring an overall negative inotropic response on the hearts.…”

Section: Discussionmentioning

confidence: 36%

Neuronostatin inhibits cardiac contractile function via a protein kinase A- and JNK-dependent mechanism in murine hearts

Hua

Ma²,

Samson³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Hua Y, Ma H, Samson WK, Ren J. Neuronostatin inhibits cardiac contractile function via a protein kinase A-and JNK-dependent mechanism in murine hearts. Am J Physiol Regul Integr Comp Physiol 297: R682-R689, 2009. First published June 24, 2009 doi:10.1152/ajpregu.00196.2009.-Neuronostatin, a newly identified peptide hormone sharing the same precursor with somatostatin, exerts multiple pharmacological effects in gastrointestinal tract, hypothalamus, and cerebellum. However, the cardiovascular effect of neuronostatin is unknown. The aim of this study was to elucidate the impact of neuronostatin on cardiac contractile function in murine hearts and isolated cardiomyocytes. Short-term exposure of neuronostatin depressed left ventricular developed pressure (LVDP), maximal velocity of pressure development (ϮdP/dt), and heart rate in Langendorff heart preparation. Consistently, neuronostatin inhibited peak shortening (PS) and maximal velocity of shortening/relengthening (ϮdL/dt) without affecting time-to-PS (TPS) and time-to-90% relengthening (TR 90) in cardiomyocytes. The neuronostatin-elicited cardiomyocyte mechanical responses were mimicked by somatostatin, the other posttranslational product of preprosomatostatin. Furthermore, the neuronostatin-induced cardiomyocyte mechanical effects were ablated by the PKA inhibitor H89 (1 M) and the Jun N-terminal kinase (JNK) inhibitor SP600125 (20 M). The PKC inhibitor chelerythrine (1 M) failed to alter neuronostatin-induced cardiomyocyte mechanical responses. To the contrary, chelerythrine, but not H89, abrogated somatostatin-induced cardiomyocyte contractile responses. Our results also showed enhanced c-fos and c-jun expression in response to neuronostatin exposure (0.5 to 2 h). Taken together, our data suggest that neuronostatin is a peptide hormone with overt cardiac depressant action. The neuronostatin-elicited cardiac contractile response appears to be mediated, at least in part, through a PKA-and/or JNK-dependent mechanism.neuronostatin; cardiomyocytes; contraction; protein kinase; cell signaling SOMATOSTATIN [ALSO NAMED SOMATOTROPIN release-inhibiting factor or growth hormone inhibiting hormone], is a peptide hormone first found in the hypothalamus. It is also expressed in neuroendocrine organs, gastrointestinal tract, thyroid and adrenal glands, liver, spleen, kidney, prostate, inflammatory, and immune cells (23). Somatostatin has been shown to be involved in the regulatory processes of endocrine system, neurotransmission, cell proliferation, hormone secretion, and cardiovascular function (17). This peptide hormone contains two active isoforms (with 14 amino acids and 28 amino acids) produced by alternative cleavage of a single preproprotein. These two isoforms of somatostatin are capable of activating five related G protein-coupled membrane receptors with different affinity (9,31,32). To date, the majority of research on somatostatin has focused on hormonal regulation in gastrointestinal and nervous systems. More recent evidence has suggested the presence of the som...

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“…Octreotide modulates neurotransmission in the central nervous system and produces mainly parasympathomimetic and sympatholytic effects on the heart, 6,22,23) and has negative inotropic and chronotropic effects on atria and positive inotropic effects on ventricles. [24][25][26] Thus, it increases not only ventricular filling time by decreasing heart rate but also ventricular contractility. In our study, octreotide increased systolic parameters such as cardiac output and left ventricular ejection fraction and decreased heart rate, probably depending on its effects stressed above studies.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Octreotide in Dilated Cardiomyopathy: An Open-label Trial in 12 Patients

et al. 2004

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SUMMARYOctreotide, a somatostatin analogue, has been found effective in the treatment of acromegalic cardiomyopathy. We investigated whether intermittent octreotide therapy had beneficial effects in patients with ischemic or idiopathic dilated cardiomyopathy, which are refractory to conventional therapy.Twelve patients with ischemic or idiopathic dilated cardiomyopathy were enrolled in the study. In addition to conventional treatment, octreotide (first 50 µg and then 25 µg three times per day for 4 days) was administered and repeated after 1, 2, and 3 months. The patients were evaluated 3 times, before and immediately after the first treatment and after 3 months of treatment, using echocardiography, exercise stress testing, ambulatory ECG, right ventricular catheterization, cardiac enzymes, and the Minnesota living with heart failure questionnaire for quality of life.There were no significant changes in parameters after the first treatment. However, after 3 months of treatment, there were significant improvements in the left ventricular ejection fraction, left ventricular posterior wall thickness, hemodynamics, exercise capacity, and quality of life. Additionally, ischemic burden and the number of ventricular premature beats also decreased slightly.Intermittent octreotide therapy led to significant improvements in patients with ischemic and idiopathic dilated cardiomyopathy refractory to conventional treatment. We believe that this therapy should be attempted as an adjunctive therapy in these patients, and that in this respect, randomized, double-blind, clinical, and large-scale studies are required before regular usage is undertaken. (Jpn Heart J 2004; 45: 613-621)

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Positive inotropic effect of somatostatin in guinea-pig ventricular muscles

Cited by 10 publications

References 32 publications

The long-term cardiovascular outcome of different GH-lowering treatments in acromegaly

The long-term cardiovascular outcome of different GH-lowering treatments in acromegaly

Neuronostatin inhibits cardiac contractile function via a protein kinase A- and JNK-dependent mechanism in murine hearts

The Effects of Octreotide in Dilated Cardiomyopathy: An Open-label Trial in 12 Patients

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