Key result
In L-NAME treated rats, atenolol and nifedipine abolished increases in systolic blood pressure and normalized cardiomyocyte hypertrophy and expression of AM, IMD, and their receptors.
Why the study?
Does atenolol or nifedipine prevent cardiomyocyte hypertrophy and normalize AM/IMD expression in NO-deficient rats?
Does atenolol or nifedipine prevent cardiomyocyte hypertrophy and normalize AM/IMD expression in NO-deficient rats?
Atenolol and nifedipine prevent cardiomyocyte hypertrophy and normalize the expression of counter-regulatory peptides (AM, IMD) and their receptors in a rat model of NO deficiency.
Does not support clinical use; leaves open translation of atenolol/nifedipine effects on hypertrophy to human NO deficiency.
BACKGROUND/AIMS: Chronic inhibition of nitric oxide (NO) synthesis is associated with hypertension, myocardial ischemia, oxidative stress and hypertrophy; expression of adrenomedullin (AM) and intermedin (IMD) and their receptor activity modifying proteins (RAMPs 1-3) is augmented in cardiomyocytes, indicating that the myocardial AM/ IMD system may be activated in response to pressure loading and ischemic insult. The aim was to examine effects on (i) parameters of cardiomyocyte hypertrophy and on (ii) expression of AM and IMD and their receptor components in NO-deficient cardiomyocytes of an intervention chosen specifically for ability to alleviate pressure loading and ischemic injury concurrently. METHODS: The NO synthesis inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 35 mg.kg(-1).day(-1)) was given to rats for 8 weeks, with/ without concurrent administration of beta-adrenoceptor antagonist, atenolol (25 mg.kg(-1).day(-1)) / calcium channel blocker, nifedipine (20mg.kg(-1).day(-1)). RESULTS: In L-NAME treated rats, atenolol / nifedipine abolished increases in systolic blood pressure and plasma AM and IMD levels and in left ventricular cardiomyocytes: (i) normalized increased cell width and mRNA expression of hypertrophic (sk-alpha-actin) and cardio-endocrine (ANP, BNP, ET) genes; (ii) normalized augmented membrane protein oxidation; (iii) normalized mRNA expression of AM, IMD, RAMP1, RAMP2 and RAMP3. CONCLUSIONS: normalization of blood pressure and membrane oxidant status together with prevention of hypertrophy and normalization of the augmented expression of AM, IMD and their receptor components in NO-deficient cardiomyocytes by atenolol / nifedipine supports involvement of both pressure loading and ischemic insult in stimulating cardiomyocyte hypertrophy and induction of these counter-regulatory peptides and their receptor components. Attenuation of augmented expression of IMD in this model cannot however be explained simply by prevention of cardiomyocyte hypertrophy.
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Bell et al. (2008) studied Nitric-oxide deficient cardiomyocyte hypertrophy. Atenolol and nifedipine vs. L-NAME alone was evaluated on Cardiomyocyte hypertrophy and expression of AM, IMD and their receptor components. In L-NAME treated rats, atenolol and nifedipine abolished increases in systolic blood pressure and normalized cardiomyocyte hypertrophy and expression of AM, IMD, and their receptors.
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