Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: roles of the peripheral vasopressin and central cholinergic systems

Cam-Etoz, Betul; Isbil-Buyukcoskun, Naciye; Ozluk, Kasim

doi:10.1590/s0100-879x2012007500027

Cited by 7 publications

(2 citation statements)

References 31 publications

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“…AM acts as a circulating hormone but it also elicits multiple biological activities in a paracrine and/or autocrine manner. Its effects are of importance for cardiovascular homeostasis, growth and development of cardiovascular tissues, modulation of the lymphatic flow, regulation of body fluids and diabetes mellitus (8)(9)(10)(41)(42)(43)(44)(45)(46)(47)(48). Systemic AM administration has been demonstrated to reduce arterial pressure, decrease peripheral vascular resistance, and increase heart rate and cardiac output (8,49).…”

Section: Am In Physiological Context Am Calcitonin-like Peptides Anmentioning

confidence: 99%

Targeting Adrenomedullin in Oncology: A Feasible Strategy With Potential as Much More Than an Alternative Anti-Angiogenic Therapy

Vázquez

Riveiro²,

Berenguer-Daizé

et al. 2021

Front. Oncol.

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The development, maintenance and metastasis of solid tumors are highly dependent on the formation of blood and lymphatic vessels from pre-existing ones through a series of processes that are respectively known as angiogenesis and lymphangiogenesis. Both are mediated by specific growth-stimulating molecules, such as the vascular endothelial growth factor (VEGF) and adrenomedullin (AM), secreted by diverse cell types which involve not only the cancerogenic ones, but also those constituting the tumor stroma (i.e., macrophages, pericytes, fibroblasts, and endothelial cells). In this sense, anti-angiogenic therapy represents a clinically-validated strategy in oncology. Current therapeutic approaches are mainly based on VEGF-targeting agents, which, unfortunately, are usually limited by toxicity and/or tumor-acquired resistance. AM is a ubiquitous peptide hormone mainly secreted in the endothelium with an important involvement in blood vessel development and cardiovascular homeostasis. In this review, we will introduce the state-of-the-art in terms of AM physiology, while putting a special focus on its pro-tumorigenic role, and discuss its potential as a therapeutic target in oncology. A large amount of research has evidenced AM overexpression in a vast majority of solid tumors and a correlation between AM levels and disease stage, progression and/or vascular density has been observed. The analysis presented here indicates that the involvement of AM in the pathogenesis of cancer arises from: 1) direct promotion of cell proliferation and survival; 2) increased vascularization and the subsequent supply of nutrients and oxygen to the tumor; 3) and/or alteration of the cell phenotype into a more aggressive one. Furthermore, we have performed a deep scrutiny of the pathophysiological prominence of each of the AM receptors (AM1 and AM2) in different cancers, highlighting their differential locations and functions, as well as regulatory mechanisms. From the therapeutic point of view, we summarize here an exhaustive series of preclinical studies showing a reduction of tumor angiogenesis, metastasis and growth following treatment with AM-neutralizing antibodies, AM receptor antagonists, or AM receptor interference. Anti-AM therapy is a promising strategy to be explored in oncology, not only as an anti-angiogenic alternative in the context of acquired resistance to VEGF treatment, but also as a potential anti-metastatic approach.

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Section: Am In Physiological Context Am Calcitonin-like Peptides Anmentioning

confidence: 99%

Targeting Adrenomedullin in Oncology: A Feasible Strategy With Potential as Much More Than an Alternative Anti-Angiogenic Therapy

Vázquez

Riveiro²,

Berenguer-Daizé

et al. 2021

Front. Oncol.

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“…It is interesting that AM has different effects on BP depending on where it is applied in the brain. 34,41 AM administration into the PVN decreases BP, 34 whereas in the lateral ventricle or NTS, AM increases BP. 42,43 Similar to AM, IMD microinjection into the lateral ventricle and NTS can cause an increase in BP, 5,7,44 but PVN microinjection of IMD decreases RSNA and BP in normal and renovascular hypertensive rats.…”

Section: Discussionmentioning

confidence: 95%

Cardiac sympathetic afferent reflex response to intermedin microinjection into paraventricular nucleus is mediated by nitric oxide and γ-amino butyric acid in hypertensive rats

Zhou

Sun

Chang

et al. 2014

Exp Biol Med (Maywood)

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Intermedin (IMD) is a member of calcitonin/calcitonin gene-related peptide (CGRP) and involves in the regulation of cardiovascular function in both peripheral tissues and central nervous system (CNS). Paraventricular nucleus (PVN) of hypothalamus is an important site in the control of cardiac sympathetic afferent reflex (CSAR) which participates in sympathetic over-excitation of hypertension. The aim of this study is to investigate whether IMD in the PVN is involved in the inhibition of CSAR and its related mechanism in hypertension. Rats were subjected to two-kidney one-clip (2K1C) surgery to induce renovascular hypertension or sham-operation (Sham). Acute experiments were carried out four weeks later under anesthesia. The CSAR was evaluated with the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to the epicardial application of capsaicin. The RSNA and MAP were recorded in sinoaortic-denervated, cervical-vagotomized and anesthetized rats. Bilateral PVN microinjection of IMD (25 pmol) caused greater decrease in the CSAR in 2K1C rats than in Sham rats, which was prevented by pretreatment with adrenomedullin (AM) receptor antagonist AM22-52, non-selective nitric oxide (NO) synthase (NOS) inhibitor L-NAME or γ-amino butyric acid (GABA)B receptor blocker CGP-35348. PVN pretreatment with CGRP receptor antagonist CGRP8-37 or GABA(A) receptor blocker gabazine had no significant effect on the CSAR response to IMD. AM22-52, L-NAME and CGP-35348 in the PVN could increase CSAR in Sham and 2K1C rats. These data indicate that IMD in the PVN inhibits CSAR via AM receptor, and both NO and GABA in the PVN involve in the effect of IMD on CSAR in Sham and renovascular hypertensive rats.

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Riluzole ameliorates learning and memory deficits in Aβ25-35-induced rat model of Alzheimer’s disease and is independent of cholinoceptor activation

Mokhtari

Baluchnejadmojarad

Nikbakht

et al. 2017

Biomedicine & Pharmacotherapy

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Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: roles of the peripheral vasopressin and central cholinergic systems

Cited by 7 publications

References 31 publications

Targeting Adrenomedullin in Oncology: A Feasible Strategy With Potential as Much More Than an Alternative Anti-Angiogenic Therapy

Targeting Adrenomedullin in Oncology: A Feasible Strategy With Potential as Much More Than an Alternative Anti-Angiogenic Therapy

Cardiac sympathetic afferent reflex response to intermedin microinjection into paraventricular nucleus is mediated by nitric oxide and γ-amino butyric acid in hypertensive rats

Riluzole ameliorates learning and memory deficits in Aβ25-35-induced rat model of Alzheimer’s disease and is independent of cholinoceptor activation

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