Original ArticleAntihypertensive Properties of a Novel Morphologic Derivative (4-tert-buthyl-2,6-bis(thiomorpholine-4-ilmethyl)phenol)Martínez-Aguilar, Luisa PhD; Lezama-Martínez, Diego BD; Orozco-Cortés, Nancy V. MD; González-Espinosa, Claudia PhD; Flores-Monroy, Jazmin PhD; Valencia-Hernández, Ignacio PhDAuthor Information *Laboratory of Pharmacology, F.E.S.-Cuautitlan, National Autonomous University of Mexico, Cuautitlan Izcalli, Mexico, Mexico; †Laboratory of Medical Chemistry, F.E.S.-Cuautitlan, National Autonomous University of Mexico, Cuautitlan Izcalli, Mexico, Mexico; ‡Laboratory of Pharmacodynamics, Superior School of Medicine, National Polytechnic Institute, D.F., Mexico, Mexico; and §Pharmacobiology Department, Center for Research and Advanced Studies, National Polytechnic Institute, D.F., Mexico, Mexico. Reprints: Luisa Martínez-Aguilar, PhD, Laboratorio de Farmacologia del Miocardio de la, F.E.S.-Cuautitlan-UNAM, Avenida 1° de mayo s/n, Col. Sta. Ma. Las Torres, Cuautitlan Izcalli, Estado de México 54760, Mexico (e-mail: [email protected]) or Ignacio Valencia-Hernández, PhD, Laboratorio de Farmacodinamia de la Escuela Superior de Medicina del IPN, Plan de San Luis y Díaz Mirón s/n, Col. Sto. Tomas, D.F. 11340, Mexico, Mexico (e-mail: [email protected]). Supported by grants from DGAPA PAPIIT IN224310-3, IN 212213-3 UNAM CATEDRA CONS-26 FES Cuautitilán, Universidad Nacional Autónoma de México and the Secretaría de Investigación y Posgrado (SIP: 20120119), Comisión de Operación y Fomento de Actividades Académicas, the Programa Institucional de Estímulo al Dèpeño de los Investigadores of the Instituto Politécnico Nacional. The authors report no conflicts of interest. Received June 23, 2015 Accepted October 22, 2015 Journal of Cardiovascular Pharmacology: March 2016 - Volume 67 - Issue 3 - p 246-251 doi: 10.1097/FJC.0000000000000340 Buy Metrics Abstract We evaluated the antihypertensive properties of 4-tert-buthyl-2,6-bis(thiomorpholine-4-ilmethyl)phenol (TBTIF). Spontaneously hypertensive rats were treated with TBTIF or captopril (both at 1 mg·kg−1·d−1 intramuscularly for 4 days), and their blood pressure (BP) was assessed. In some experiments, concentration response curves to angiotensin I or angiotensin II were generated in rat aortic rings and in the absence or presence of Ang-(1-7), NG-monomethyl L-arginine, or both; additionally, the angiotensin-converting enzyme (ACE) and ACE2 mRNA levels were quantified in the aortic rings using reverse transcription–polymerase chain reaction. TBTIF diminished BP and reduced angiotensin I- or angiotensin II-induced vasoconstriction. The presence of Ang-(1-7) induced a greater reduction in vasoconstriction, and this effect was reversed by L-NG-monomethyl arginine. Moreover, TBTIF decreased the mRNA of ACE and increased the mRNA of ACE2. In conclusion, TBTIF diminished rat BP through nitric oxide-dependent and nitric oxide-independent mechanisms. In contrast to captopril, TBTIF exhibits better antihypertensive properties through mechanisms that involve ACE2. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.