Chronic blockade of angiotensin II AT1-receptors increased cell-to-cell communication, reduced fibrosis and improved impulse propagation in the failing heart.
BACKGROUND
The influence of chronic administration of losartan on gap junction conductance (gj), conduction velocity and interstitial fibrosis was investigated in the failing heart of 4-month-old cardiomyopathic hamsters (TO-2). After two months of administration of losartan (25 mg/kg/day/po) the number of cell pairs showing very low values of gj (28 nS) was significantly reduced whereas the group of cell pairs with larger values of gj (18-45 nS) was significantly increased. The conduction velocity measured with intracellular microelectrodes in the wall of the left ventricle was enhanced from 38+2.3 cm/s (n=25) (control) to 49+2 cm/s (n=24) (p<0.05) after losartan administration. Moreover, the number of ventricular fibres showing non-propagated action potentials was significantly decreased (p<0.05) by losartan. The % area of interstitial fibrosis measured in the wall of the left ventricle was reduced from 22+1.4% (n=18) to 14+1.3% (n=18) (p<0.05) after losartan administration.


CONCLUSIONS
Chronic blockade of angiotensin II type 1 receptors increased gj in the failing heart. Moreover, the conduction velocity was enhanced in part by the increase of gj and in part by the decrease of interstitial fibrosis and structural remodelling.
De Mello
Walmor C
WC
Department of Pharmacology, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936-5067, USA. wmello@rcm.upr.edu
Specht
Philip
P
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002450:Cell Communication / Q000187:drug effects; D006224:Cricetinae; D005355:Fibrosis / Q000188:drug therapy; D017629:Gap Junctions / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects*; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008647:Mesocricetus; D009431:Neural Conduction / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan