Systemic and regional hemodynamic and cardiac remodeling effects of candesartan in dilated cardiomyopathic hamsters with advanced congestive heart failure.
The effects of the selective angiotensin II type 1 receptor antagonist candesartan on cardiac, systemic, and regional hemodynamics and on cardiac, pulmonary, and hepatic histomorphometry were investigated in cardiomyopathic hamsters (CMHs), Bio TO-2 dilated strain, with advanced congestive heart failure (CHF). Two groups were treated orally with candesartan cilexetil at 22 or 50 mg/kg/d from 190 days of age and compared with a control group (38 animals/group). Investigations were performed at 225, 255, and 285 days of age. Left ventricle (LV) and systemic blood pressures and cardiac output and mesenteric and femoral blood flows were measured in anesthetized animals. LV cavity area, LV and right ventricle (RV) wall thickness and collagen density, and pulmonary and hepatic congestion were assessed. Compared with the control group, candesartan did not modify cardiac hemodynamics but significantly and dose-dependently decreased systemic vascular resistances (on average: -23 and -32% after 22 and 50 mg/kg, respectively) and increased stroke volume (+32 and +42%) and cardiac output (+27 and +34%). Candesartan did not modify mesenteric vascular resistances and blood flow but significantly and dose-dependently decreased femoral vascular resistances (-19 and -33%) and increased femoral blood flow (+33 and +43%). Candesartan significantly decreased LV cavity area (-14 and -8%) and LV (-15 and -31%) and RV (-16 and -24%) collagen density but did not modify LV and RV wall thickness. Candesartan decreased pulmonary congestion at 255 and 285 days of age but did not modify hepatic congestion. In CMHs with advanced CHF, candesartan cilexetil improves systemic and femoral hemodynamics, partly reverses cardiac remodeling, and decreases pulmonary congestion.
Laboratoire de Pharmacologie Expérimentale et Clinique, UPRES EA 3194 Groupe de Recherche Cardio-Vasculaire, Faculté de Médecine, 2 Avenue du Professeur Léon Bernard, CS 34317, 35043 Rennes Cedex, France.
Sonia
S
Goineau
Sophie
S
Nisse-Durgeat
Danielle
D
Pape
Pascal
P
Guillo
Marie-Paule
MP
Ramée
Eric
E
Bellissant
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000188:drug therapy*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles; D020257:Ventricular Remodeling
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C077793:candesartan cilexetil