title: Long-term organ protection by doxazosin and/or quinapril as antihypertensive therapy.
abstract: BACKGROUND
  Even with optimal blood pressure control, organ protection may also depend on the selected therapeutic regime. Angiotensin-converting enzyme inhibitors have been shown to provide excellent organ protection in hypertension, and may show dose-dependent protective effects. Adrenergic alpha blockers have been associated with an increased rate of heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and Vasodilator-Heart Failure Trial (V-HeFT). This has been related to a proapoptotic effect of this drug in cardiomyocytes. Our purpose is to compare the heart and renal protection of a high quinapril dose, with a combined low quinapril dose plus doxazosin, in an animal model of chronic hypertension.
  
  
  METHODS
  Uninephrectomized spontaneously hypertensive 12-week-old rats were treated for 36 weeks with either quinapril or a combination of doxazosin plus a low quinapril dose. Tight blood pressure control was achieved with both treatments. Renal and cardiac protection was assessed by different parameters, and cardiac apoptosis was evaluated by active caspase-3, apoptotic protein and heat shock protein levels. Untreated hypertensive and normotensive rats were included as controls.
  
  
  RESULTS
  Both treatments showed significant heart and renal protection compared with untreated animals. Both therapeutic regimes showed similar protection in renal and cardiac pathology, coronary media fibrosis, myocardial apoptosis and cardiac index. Proteinuria and left ventricular hypertrophy regression were significantly lower in the quinapril group compared with the combined treatment group.
  
  
  CONCLUSIONS
  Blood pressure control with a high quinapril dose provided higher organ protection than a combined therapy with a lower quinapril dose. This effect was not due to a deleterious effect of doxazosin.
authors.affiliation: Renal and Vascular Pathology Laboratory, Fundacion Jimenez Diaz-Universidad Autonoma, Madrid-Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Gallego-Delgado
authors.forename: Alberto
authors.initials: A
authors.lastname: Lazaro
authors.forename: Dulcenombre
authors.initials: D
authors.lastname: Gomez-Garre
authors.forename: Julio I
authors.initials: JI
authors.lastname: Osende
authors.forename: Maria L
authors.initials: ML
authors.lastname: Gonzalez-Rubio
authors.forename: Marta
authors.initials: M
authors.lastname: Herraiz
authors.forename: Félix
authors.initials: F
authors.lastname: Manzarbeitia
authors.forename: José
authors.initials: J
authors.lastname: Fortes
authors.forename: Arturo
authors.initials: A
authors.lastname: Fernandez-Cruz
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002908:Chronic Disease; D004195:Disease Models, Animal; D017292:Doxazosin / Q000009:adverse effects / Q000494:pharmacology*; D005355:Fibrosis / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D032383:Myocytes, Cardiac / Q000473:pathology; D000077583:Quinapril; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044005:Tetrahydroisoquinolines / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D044005:Tetrahydroisoquinolines; D017292:Doxazosin; D000077583:Quinapril