Objective: To evaluate the role of arginine vasopressin (AVP) in the normal and post-myocardial infarction (post-MI) hearts, and to investigate whether chronic AVP receptor antagonism can attenuate post-infarct ventricular remodeling.
Background: A number of neurohormones, like norepinephrine and angiotensin II, have detrimental effects in heart failure (HF) and inhibiting them is beneficial. AVP shares some important properties with these hormones and is activated in HF. However, its role in the syndrome of HF, especially the effect of AVP inhibition, is largely undefined.
Methods and results: Effects of AVP-V1a and AVP-V2 receptor stimulation on normal rat cardiomyocyte contractile function, intracellular calcium [Ca2+]i, inositol 3 phosphate (IP3) generation and cell survival were studied. In post-MI rats, AVP receptor function was assessed in cardiomyocytes as well as isolated working hearts. AVP receptor total number (ligand binding) and mRNA levels (RT-PCR) were measured in myocytes. Finally, the effects of chronic AVP-V1a blockade were assessed in post-MI rats using echo and morphometry to measure ventricular remodeling. Normal cardiomyocytes showed a dose-dependent increase in myocyte contractile function, [Ca2+]i, and IP3 generation in response to AVP-V1a receptor stimulation. AVP-V2 agonists had no effect. Cells from MI hearts showed reduced inotropic response to AVP-V1a stimulation. Myocyte AVP-V1a receptor number and receptor mRNA were decreased. Prolonged exposure to AVP reduced cellular viability. However, chronic AVP-V1a blockade did not attenuate structural remodeling or improve function in post-MI hearts.
Conclusions: Isolated adult rat cardiomyocytes bear AVP-V1a receptors that mediate inotropic effects through the IP3 pathway. These receptors are functionally and numerically downregulated in the post-MI remodeled hearts. Despite evidence that AVP is cytotoxic to cells, chronic AVP-V1a receptor blockade does not attenuate post-MI ventricular remodeling in this model. Thus, AVP may not play a major role in the structural progression of HF.