title: Ascorbic acid decreases the binding affinity of the AT1 receptor for angiotensin II.
abstract: BACKGROUND
  Ascorbic acid is an essential vitamin and a powerful antioxidant. Many studies have highlighted the benefits of ascorbic acid for chronic cardiovascular diseases such as hypertension in which angiotensin II (Ang II) plays an significant role. We therefore hypothesized that ascorbic acid could modify the pharmacological properties of the AT(1) receptor for Ang II.
  
  
  METHODS
  Binding studies and Ca(2+) mobilization studies were performed with HEK293 cells stably expressing the AT(1) receptor for Ang II. Smooth muscle contraction studies were performed with rabbit aorta strips that endogenously express the AT(1) receptor.
  
  
  RESULTS
  Scatchard analysis revealed that ascorbic acid decreased the binding affinity of the AT(1) receptor without modifying its maximal binding capacity. Ascorbic acid did not modify the binding affinity of the AT(2) receptor for Ang II or of the UT receptor for urotensin II. In single-cell Ca(2+) imaging assays, ascorbic acid reduced the frequency of intracellular Ca(2+) oscillations induced by a low dose of Ang II. In functional assays, ascorbic acid significantly diminished the contraction of rabbit aorta pre-contracted with Ang II but not those pre-contracted with urotensin II.
  
  
  CONCLUSIONS
  Ascorbic acid decreases the binding affinity of the AT(1) receptor. These results offer a mechanistic explanation for the reported blood pressure lowering effect of ascorbic acid.
authors: Department of Pharmacology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada.
authors: Patrice C
authors: PC
authors: Leclerc
authors: Christophe D
authors: CD
authors: Proulx
authors: Guillaume
authors: G
authors: Arguin
authors: Simon
authors: S
authors: Bélanger
authors: Fernand
authors: F
authors: Gobeil
authors: Emanuel
authors: E
authors: Escher
authors: Richard
authors: R
authors: Leduc
authors: Gaétan
authors: G
authors: Guillemette
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D001205:Ascorbic Acid