Long-term organ protection by doxazosin and/or quinapril as antihypertensive therapy.
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.
Gallego-Delgado
Julio
J
Renal and Vascular Pathology Laboratory, Fundacion Jimenez Diaz-Universidad Autonoma, Madrid-Spain.
Lazaro
Alberto
A
Gomez-Garre
Dulcenombre
D
Osende
Julio I
JI
Gonzalez-Rubio
Maria L
ML
Herraiz
Marta
M
Manzarbeitia
Félix
F
Fortes
José
J
Fernandez-Cruz
Arturo
A
Egido
Jesús
J
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*
D000959:Antihypertensive Agents; D044005:Tetrahydroisoquinolines; D017292:Doxazosin; D000077583:Quinapril