title: Revelation on the potency of α(1) -blockers - parallel blockade of angiotensin II receptor: a new finding.
abstract: BACKGROUND
  The problem of hypertension has gained enormous proportions in the past decade. Multifactorial etiology and complex pathophysiology of the disease has rendered the treatment of the disease a hard task. Sympathetic nervous system and the renin-angiotensin-aldosterone system are primary contributors of blood pressure homeostasis.
  
  
  OBJECTIVE
  Structural similarities were identified among AT(1) and α(1)-antagonists, initiating a speculation that α(1)-antagonists could possibly block the AT(1) receptor and vice-versa.
  
  
  METHODS
  To corroborate this speculation, we screened prototypical α(1)-antagonists such as prazosin, doxazosin, and terazosin for antagonism of angiotensin II on rat aortic strips. We also examined the AT(1) antagonists losartan, valsartan, and olmesartan for their possible antagonistic effect, on contractions of rat aortic strips induced by phenylephrine.
  
  
  RESULTS
  To our astonishment, we found that prazosin and its analogs which have been reported to have α(1)-antagonistic activity only, were able to shift concentration response curves of angiotensin II.
  
  
  CONCLUSIONS
  Our findings suggest that the potent antihypertensive effect of prazosin-type α(1)-antagonists is not purely due to α(1)-receptor blocking activity of these compounds but also due to blockade of AT(1) receptors. This finding may lead to the development of more potent dual inhibitors which would prove to be of immense value in the control of the scourge of hypertension.
authors.affiliation: Pharmacy Department, Faculty of Technology and Engineering, Kalabhavan, The M. S. University of Baroda, Vadodara, Gujarat, India. mryadav11@yahoo.co.in
authors.forename: M R
authors.initials: MR
authors.lastname: Yadav
authors.forename: H P
authors.initials: HP
authors.lastname: Gandhi
authors.forename: P P
authors.initials: PP
authors.lastname: Naik
authors.forename: R
authors.initials: R
authors.lastname: Giridhar
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D017292:Doxazosin / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D011224:Prazosin / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D018340:Receptors, Adrenergic, alpha-1; D013777:Tetrazoles; D014665:Vasodilator Agents; D000068756:Valsartan; C041226:Terazosin; C437965:olmesartan; D014633:Valine; D019808:Losartan; D017292:Doxazosin; D011224:Prazosin