Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension

Petkov, Ventzislav; Mosgoeller, Wilhelm; Ziesche, Rolf; Raderer, Markus; Stiebellehner, Leopold; Vonbank, Karin; Funk, Georg‐Christian; Hamilton, Gerhard; Novotny, Clemens; Burian, Bernhard; Block, Lutz H.

doi:10.1172/jci17500

Cited by 304 publications

(111 citation statements)

References 35 publications

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“…Scintillography of PAH patients given intravenous radiolabeled 123 I-labelled VIP appears to confirm uptake of the peptide in the lung (Petkov et al, 2003). An exploratory open-label study of VIP 200micrograms given as 4 single inhalations per day for 3 months in 8 PAH patients showed a 40% reduction in pulmonary vascular resistance, from 1,009 ± 475 dyne/s/cm 5 to 586 ± 165 dyne/s/cm 5 (Petkov et al, 2003).…”

Section: Accepted Manuscriptmentioning

confidence: 91%

“…An exploratory open-label study of VIP 200micrograms given as 4 single inhalations per day for 3 months in 8 PAH patients showed a 40% reduction in pulmonary vascular resistance, from 1,009 ± 475 dyne/s/cm 5 to 586 ± 165 dyne/s/cm 5 (Petkov et al, 2003). The 6-minute walk distance increased by 113m, from 296±138 to 409±102m (p<0.01).…”

Section: Accepted Manuscriptmentioning

confidence: 96%

“…Preclinical and open-label studies in humans support a role for vasoactive intestinal peptide (VIP) in the regulation of pulmonary vascular homeostasis (Leuchte et al, 2008;Petkov et al, 2003;Saga & Said, 1984;Said et al, 2007). VIP is a 28 amino acid peptide that has been shown to relax pulmonary vascular smooth muscle in several mammalian species in vitro (Saga & Said, 1984) and inhibits proliferation of pulmonary vascular smooth muscle cells from patients with PAH (Petkov et al, 2003).…”

Section: Vasoactive Intestinal Peptide (Aviptadil)mentioning

confidence: 99%

“…VIP is a 28 amino acid peptide that has been shown to relax pulmonary vascular smooth muscle in several mammalian species in vitro (Saga & Said, 1984) and inhibits proliferation of pulmonary vascular smooth muscle cells from patients with PAH (Petkov et al, 2003). VIP receptors are expressed in pulmonary arterioles and are more abundant in endstage disease tissue from IPAH patients (Petkov et al, 2003).…”

Section: Vasoactive Intestinal Peptide (Aviptadil)mentioning

confidence: 99%

See 3 more Smart Citations

Why drugs fail in clinical trials in pulmonary arterial hypertension, and strategies to succeed in the future

Lythgoe

Rhodes

Ghataorhe

et al. 2016

Pharmacology & Therapeutics

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The past three decades have witnessed a welcome expansion of the therapeutic armamentarium for the management of pulmonary arterial hypertension (PAH). But against this backdrop there have been some notable disappointments in drug development. Here we use these as case studies to emphasise the importance of informed drug target selection, the early evaluation of dose-response relationships in human studies and the value of deep-phenotyping of patients in clinical studies to better understand inter-individual variation in patient response. The integration of 'omics' technologies and advanced clinical imaging offer the potential to reduce the risk, and so cost, of drug development in PAH and bring much needed new medicines to those patients most likely to benefit with greater efficiency.

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Section: Accepted Manuscriptmentioning

confidence: 91%

Section: Accepted Manuscriptmentioning

confidence: 96%

Section: Vasoactive Intestinal Peptide (Aviptadil)mentioning

confidence: 99%

Section: Vasoactive Intestinal Peptide (Aviptadil)mentioning

confidence: 99%

See 2 more Smart Citations

Why drugs fail in clinical trials in pulmonary arterial hypertension, and strategies to succeed in the future

Lythgoe

Rhodes

Ghataorhe

et al. 2016

Pharmacology & Therapeutics

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“…VIP-Mangel ist im Lungengewebe von Patienten mit idiopathischer PAH (IPAH) beschrieben worden. In einer vorläufig untersuchten Fallserie zeigten 8 Patienten mit IPAH, die mit inhalativem VIP in Tagesdosen von 200 µg in vier einzelnen Inhalationen behandelt wurden, eine deutliche klinische und hämodynamische Verbesserung [18]. Eine kürzlich durchgeführte doppelblinde Studie zu inhalativem VIP fiel allerdings negativ aus.…”

Section: Therapie Der Pulmonal-arteriellen Hypertonieunclassified

Zukunftsperspektiven auf dem Gebiet der pulmonal-arteriellen Hypertonie

Rubin¹

2016

Kompass Pneumol

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In einem bemerkenswert kurzen Zeitraum hat sich die pulmonal-arteriellen Hypertonie (PAH) von einer Krankheit unbekannter Pathogenese ohne wirksame Therapie zu einem pathologischen Zustand entwickelt, dessen zelluläre und molekulare Grundlagen immer besser bekannt sind und für den mittlerweile drei Therapieklassen zur Verfügung stehen. Dennoch bleibt die PAH unheilbar und ist oft refraktär gegenüber medikamentöser Therapie, was die Notwendigkeit weiterer Forschung unterstreicht. In diesem Bei- trag werden einige der meistbeachteten Forschungsansätze zur Pathogenese, Diagnose und Überwachung sowie neue Therapieansätze vorgestellt, die hoffentlich künftig Einzug in die klinische Praxis halten.

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Endogenous Vasoactive Peptides

Webb

Ksander²

2010

Burger's Medicinal Chemistry and Drug Discovery

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The control of vasomotor tone regulates the overall cardiovascular system and its responses to physiological and pathophysiological stress. It provides differential blood flow to regional vascular beds under normal physiologic conditions, at times of normal stress, such as exercise, and during conditions of pathological stress, such as congestive heart failure. Although the vascular system regulates many of its functions at the site of the blood vessel itself, other factors that may control vascular tone include the autonomic nervous system, circulating hormones functioning in an endocrine role, and reflex metabolic control. Many newly discovered peptides were found to be widespread in autonomic and sensory neurons innervating the vasculature, and they possess potent vasoactive effects on many blood vessels. Vasoactive peptides have been shown to play an important role in many pathological situations, for example, asthma, arthritis, vascular headaches, hypertension, and other cardiovascular diseases. In this chapter, we will outline the evidence for the different actions of various vasoactive peptides, their interaction with other systems, the possible role they have in diseases, and the present and future therapeutic use of vasoactive peptide agonists and antagonists.

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Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension

Abstract: Conflict of interest:The authors have declared that no conflict of interest exists. Nonstandard abbreviations used: primary pulmonary hypertension (PPH); vasoactive intestinal peptide (VIP); pulmonary artery smooth muscle cells (PASMCs); mean pulmonary arterial pressure (MPAP).

Cited by 304 publications

References 35 publications

Why drugs fail in clinical trials in pulmonary arterial hypertension, and strategies to succeed in the future

Why drugs fail in clinical trials in pulmonary arterial hypertension, and strategies to succeed in the future

Zukunftsperspektiven auf dem Gebiet der pulmonal-arteriellen Hypertonie

Endogenous Vasoactive Peptides

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