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We thank the Animal Care Facility of the Faculty of Ciencias de la Salud (URJC); in addition, we also thank the contribution of Daniel Horrillo, Ismael Velasco and L. Alejandro Meca for their technical assistance. The authors dedicate this work to the memory of Dr. Jose Vicente Perez-Giron, who died on 29th March 2016. This work was supported by the Spanish Ministerio de Ciencia, Innovacion y Universidades (SAF2015-69294-R and SAF2016-80305-P), Instituto de Salud Carlos III (CIBER de Enfermedades Cardiovasculares, CB16.11.00286), Comunidad de Madrid (B2017/BMD-3676) and Fondo Europeo de Desarrollo Regional (FEDER) a way to build Europe.

Analysis of institutional authors

Hernanz, RAuthorMartin, AAuthorBarrus, MtAuthorGonzalez-Carnicero, ZAuthorAlonso, MjCorresponding Author

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Article

Pioglitazone Modulates the Vascular Contractility in Hypertension by Interference with ET-1 Pathway

Publicated to:Scientific Reports. 9 (16461): 16461- - 2019-11-11 9(16461), DOI: 10.1038/s41598-019-52839-6

Authors: Palacios-Ramirez, Roberto; Hernanz, Raquel; Martin, Angela; Perez-Giron, Jose V; Barrus, Maria T; Gonzalez-Carnicero, Zoe; Aguado, Andrea; Jaisser, Frederic; Briones, Ana M; Salaices, Mercedes; Alonso, Maria J

Affiliations

Ciber Enfermedades Cardiovasc, Madrid, Spain - Author
Paris VI Univ, INSERM, U1138, Cordeliers Inst, Paris, France - Author
Univ Autonoma Madrid, Hosp Paz La IdiPaz, Inst Invest, Dept Farmacol,Fac Med, Madrid, Spain - Author
Univ Rey Juan Carlos, Fac Ciencias Salud, Dept Ciencias Basicas Salud, Alcorcon, Spain - Author

Abstract

Endothelin-1 (ET-1) is an important modulator of the vascular tone and a proinflammatory molecule that contributes to the vascular damage observed in hypertension. Peroxisome-proliferator activated receptors-gamma (PPAR gamma) agonists show cardioprotective properties by decreasing inflammatory molecules such as COX-2 and reactive oxygen species (ROS), among others. We investigated the possible modulatory effect of PPAR. activation on the vascular effects of ET-1 in hypertension. In spontaneously hypertensive rats (SHR), but not in normotensive rats, ET-1 enhanced phenylephrine-induced contraction through ETA by a mechanism dependent on activation of TP receptors by COX-2-derived prostacyclin and reduction in NO bioavailability due to enhanced ROS production. In SHR, the PPAR gamma agonist pioglitazone (2.5 mg/Kg.day, 28 days) reduced the increased ETA levels and increased those of ETB. After pioglitazone treatment of SHR, ET-1 through ETB decreased ROS levels that resulted in increased NO bioavailability and diminished phenylephrine contraction. In vascular smooth muscle cells from SHR, ET-1 increased ROS production through AP-1 and NF kappa B activation, leading to enhanced COX-2 expression. These effects were blocked by pioglitazone. In summary, in hypertension, pioglitazone shifts the vascular ETA/ETB ratio, reduces ROS/COX-2 activation and increases NO availability; these changes explain the effect of ET-1 decreasing phenylephrine-induced contraction.

Keywords

Angiotensin-iiAnimalAnimalsAntidiabetic agentBlood-pressureCardiac-hypertrophyCytologyDrug effectEndothelin 1Endothelin-1Endothelin-receptor antagonistHypertensionHypoglycemic agentsMaleMetabolismMolecular-mechanismsMuscle contractionMuscle, smooth, vascularMyocytes, smooth muscleNf-kappa-bOxidative stressPathologyPenile arteriesPeroxisome proliferator activated receptor gammaPioglitazonePpar gammaRatRatsRats, inbred shrRats, wistarReactive oxygen metaboliteReactive oxygen speciesSmooth muscle cellSmooth-muscle-cellsSpontaneously hypertensive ratSuperoxide-productionVascular smooth muscleWistar rat

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Scientific Reports due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2019, it was in position 17/71, thus managing to position itself as a Q1 (Primer Cuartil), in the category Multidisciplinary Sciences.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 3.48, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-14, the following number of citations:

  • WoS: 18
  • Scopus: 22
  • Europe PMC: 11
  • OpenCitations: 19

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-14:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 22.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 22 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.35.
  • The number of mentions on the social network X (formerly Twitter): 2 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: France.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author () and Last Author (Alonso Gordo, María Jesús).

the author responsible for correspondence tasks has been Alonso Gordo, María Jesús.