{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:10:44Z","timestamp":1777392644184,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014064","name":"Universidad de Salamanca","doi-asserted-by":"publisher","award":["18K233\/463AC01; 18K251\/463AC01"],"award-info":[{"award-number":["18K233\/463AC01; 18K251\/463AC01"]}],"id":[{"id":"10.13039\/501100014064","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>The vascular 5-HT sympatho-modulation may involve inhibitory or potentiating pathways: nitric oxide (NO), endothelium-dependent hyperpolarization (EDH)-K+ channels, prostanoids, angiotensin II (Ang-II), or endothelin. Compared to males, female rats show differences in the serotonergic sympatho-regulation; therefore, we aimed to study the involvement of indirect pathways via 5-HT1D-mediated inhibition and 5-HT2A\/3-mediated potentiation of vascular noradrenergic neurotransmission in females. An i.v. bolus of different inhibitors\/blockers of modulators\/mediators (NO, K+ channels, prostanoids, Ang-II, or endothelin) was administered prior to the infusion of the agonists, L-694,247 (5-HT1D), TCB-2 (5-HT2A), or 1-PBG (5-HT3), in female pithed rats. In these conditions, the vascular sympathetic outflow was electrically stimulated to assess the vasopressor responses. The L-694,247 vascular sympatho-inhibition was abolished by a non-selective K+ channel blocker, tetraethylammonium. The 1-PBG sympatho-excitatory vascular effect was not modified by any of the inhibitors tested, whereas TCB-2 sympatho-potentiation was blocked solely by losartan (Ang-II type 1 receptor antagonist). Moreover, Ang-II levels were increased after TCB-2 infusion in females. The EDH pathway mediates the 5-HT1D-induced sympatho-inhibition, while the 5-HT2A-evoked sympatho-excitatory effect is associated with Ang-II. In contrast, the 5-HT3 sympatho-potentiation does not involve any indirect pathway. These findings advance current understanding of the complex interactions between 5-HT and vascular homeostasis in female rats.<\/jats:p>","DOI":"10.3390\/ijms26199614","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T15:20:38Z","timestamp":1759332038000},"page":"9614","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Angiotensin II and EDH Pathways Underlie the Vascular Sympatho-Modulation by 5-HT in Female Rats"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6712-804X","authenticated-orcid":false,"given":"Ana\u00efs Clara","family":"Terol-\u00dabeda","sequence":"first","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2344-4523","authenticated-orcid":false,"given":"Juan Francisco","family":"Fern\u00e1ndez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7509-1232","authenticated-orcid":false,"given":"Asunci\u00f3n","family":"Mor\u00e1n","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6140-4322","authenticated-orcid":false,"given":"M\u00f3nica","family":"Garc\u00eda-Domingo","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5252-9470","authenticated-orcid":false,"given":"Jos\u00e9 \u00c1ngel","family":"Garc\u00eda-Pedraza","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"ref_1","first-page":"232","article-title":"Recent advances in understanding serotonin regulation of cardiovascular function","volume":"10","author":"Fligny","year":"2024","journal-title":"Trends Mol. 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