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Vascular smooth muscle cells (SMCs) are major components of blood vessels and are involved in physiologic and pathophysiologic conditions. In healthy vessels, vascular SMCs contribute to vasotone and regulate blood flow by cyclic nucleotide intracellular pathways. However, vascular SMCs lose their contractile phenotype under pathological conditions and alter contractility or signalling mechanisms, including cyclic nucleotide compartmentation. In the present review, we focus on compartmentalized signaling of cyclic nucleotides in vascular smooth muscle. A deeper understanding of these mechanisms clarifies the most relevant axes for the regulation of vascular tone. Furthermore, this allows the detection of possible changes associated with pathological processes, which may be of help for the discovery of novel drugs.<\/jats:p>","DOI":"10.3390\/jcdd9010004","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T02:01:19Z","timestamp":1640224879000},"page":"4","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["PDE-Mediated Cyclic Nucleotide Compartmentation in Vascular Smooth Muscle Cells: From Basic to a Clinical Perspective"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4752-6398","authenticated-orcid":false,"given":"Margarida","family":"Lorigo","sequence":"first","affiliation":[{"name":"Health Sciences Research Centre (CICS-UBI), University of Beira Interior, 6200-506 Covilha, Portugal"},{"name":"Department of Medical Sciences, Faculty of Health Sciences (FCS-UBI), University of Beira Interior, 6200-506 Covilha, Portugal"}]},{"given":"Nelson","family":"Oliveira","sequence":"additional","affiliation":[{"name":"UDI-IPG, Research Unit for Inland Development, Department of Social Sciences and Communication, Polytechnic Institute of Guarda, 6300-654 Guarda, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4823-5701","authenticated-orcid":false,"given":"Elisa","family":"Cairrao","sequence":"additional","affiliation":[{"name":"Health Sciences Research Centre (CICS-UBI), University of Beira Interior, 6200-506 Covilha, Portugal"},{"name":"Department of Medical Sciences, Faculty of Health Sciences (FCS-UBI), University of Beira Interior, 6200-506 Covilha, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Herrmann, J., Babic, M., T\u00f6lle, M., Van Der Giet, M., and Schuchardt, M. 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