Molecular basis of regression of cardiac hypertrophy.
Cardiac hypertrophy due to a chronic mechanical overload puts into play a biologic cascade, including a trigger (the mechanical stretch), a transmitter (very likely to be the phosphoinositol pathway), and the final target (which is the DNA). The permanent changes in genetic expression resulting from the activation of this cascade allows the heart to produce normal active tension at a lower cost in terms of energy expenditure. The process is reversible, providing the treatment reduces the real load on the heart--i.e., not only the peripheral resistances but also the aortic impedance--during a period of time that has to be several times the half-life of cardiac proteins, and also that the treatment has an effect on the detrimental consequences of cardiac hypertrophy, namely, the systolic and diastolic dysfunction and the incidence of arrhythmias. In this report semisenescent spontaneously hypertensive rats were treated for 3 months with the converting enzyme inhibitor trandolapril. The treatment had a rather modest effect on blood pressure but resulted in a pronounced reduction in cardiac hypertrophy and in cardiac fibrosis, an improved coronary reserve, and attenuated both the effects of anoxia on the left ventricular diastolic compliance and the incidence of ventricular arrhythmias.
Chevalier
B
B
U127-INSERM, Hopital Lariboisière, Paris, France.
Callens-el Amrani
F
F
Heymes
C
C
Swynghedauw
B
B
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D016277:Ventricular Function, Left / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C052035:trandolapril