Experimental diabetes and left ventricular hypertrophy: effects of beta-receptor blockade.
BACKGROUND
Left ventricular hypertrophy involves growth of cardiomyocytes, as well as remodeling of extracellular matrix proteins (ECMPs). Several metabolic abnormalities may be triggered secondary to hyperglycemia in diabetes. The effects of combined supravalvular aortic banding and diabetes mellitus on the rat heart were investigated in order to detect possible synergistic effects of these two conditions. Moreover, this study focused on the impact of beta-adrenoceptor blockade with carvedilol (C) on the expression of ECMPs.


METHODS
Sixty male Wistar rats were allocated to six groups: control (CON), CON+C, streptozotocin (65 mg/kg iv)-induced diabetes (D), D+C, aortic stenosis (AS)+D and AS+D+C. Follow-up was 6 weeks.


RESULTS
Relative left ventricular weight was elevated and body weight was decreased in D, AS+D and AS+D+C rats (P<.05 vs. CON). Diabetes elevated cardiomyocyte widths, perivascular/interstitial fibrosis (P<.01 each), as well as ECMPs: collagen I/fibronectin/laminin were 3.4-fold/4.1-fold/1.5-fold elevated in D rats and further increased (4.6-fold/5.9-fold/1.9-fold) in AS+D rats (P<.01 vs. CON). Heart rate and blood pressure decreased in D and AS+D rats (P<.05 vs. CON). Carvedilol application attenuated the overexpression of ECMPs.


CONCLUSIONS
Beta-adrenoceptor blockade results in regression of the hypertrophic phenotype and in decrease of ECMP in rats with experimental diabetes and in animals with combined chronic pressure overload and hyperglycemia. These results represent a new mechanism of carvedilol that may contribute to the observed beneficial effects in heart failure.
Institute of Clinical Pharmacology and Toxicology, Benjamin Franklin Medical Center, Freie Universität Berlin, Garystr. 5, D-14195 Berlin, Germany. dgrimm@zedat.fu-berlin.de
Daniela
D
Grimm
Hans C
HC
Jabusch
Peter
P
Kossmehl
Michaela
M
Huber
Sabine
S
Fredersdorf
Daniel P
DP
Griese
Bernhard K
BK
Krämer
Eckhard P
EP
Kromer
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D002227:Carbazoles / Q000627:therapeutic use; D000077261:Carvedilol; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D011412:Propanolamines / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D016326:Extracellular Matrix Proteins; D011412:Propanolamines; D000077261:Carvedilol