title: Antihypertensive Properties of a Novel Morphologic Derivative (4-tert-buthyl-2,6-bis(thiomorpholine-4-ilmethyl)phenol).
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), N(G)-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-N(G)-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.
authors.affiliation: *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.
authors.forename: Luisa
authors.initials: L
authors.lastname: Martínez-Aguilar
authors.forename: Diego
authors.initials: D
authors.lastname: Lezama-Martínez
authors.forename: Nancy V
authors.initials: NV
authors.lastname: Orozco-Cortés
authors.forename: Claudia
authors.initials: C
authors.lastname: González-Espinosa
authors.forename: Jazmin
authors.initials: J
authors.lastname: Flores-Monroy
authors.forename: Ignacio
authors.initials: I
authors.lastname: Valencia-Hernández
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011918:Rats, Inbred SHR; D015854:Up-Regulation; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: C000598409:4-tert-butyl-2,6-bis(thiomorpholin-4-ylmethyl)phenol; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D009025:Morpholines; D010636:Phenols; D012333:RNA, Messenger; D014665:Vasodilator Agents; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2