Evidence for a vasopressin system in the rat heart

Traditionally, a hypothalamo-neurohypophysial system is thought to be the e xclusive source of arginine vasopressin (AVP), a potent antidiuretic, vasoc onstricting, and growth-stimulating neuropeptide. We have identified de nov o synthesis of AVP in the heart as well as release of the hormone into the cardiac effluents. Specifically, molecular cloning of sequence tags amplifi ed from isolated, buffer-perfused, and pressure-overloaded rat hearts allow ed the detection of cardiac AVP mRNA, Subsequent experiments revealed a pro minent induction of AVP mRNA (peak at 120 minutes, 59-fold, P<0.01 versus b aseline) and peptide (peak at 120 minutes, Ii-fold, P<0.01 versus baseline) in these isolated hearts. Newly induced vasopressin peptide was localized most prominently to endothelial cells and vascular smooth muscle cells of a rterioles and perivascular tissue using immunohistochemistry. In addition t o pressure overload, nitric oxide (NO) participated in these alterations, b ecause inhibition of NO synthase by N-omega-nitro-L-arginine methyl ester m arkedly depressed cardiac AVP mRNA and peptide induction. Immediate cardiac effects related to cardiac AVP induction in isolated, perfused, pressure-o verloaded hearts appeared to be coronary vasoconstriction and impaired rela xation. These functional changes were observed in parallel with AVP inducti on and largely prevented by addition of a V-1 receptor blocker (10(-8) mol/ L [deamino-Pen(1), O-Me-Tyr(2), Arg(8)]-vasopressin) to the perfusion buffe r. Even more interesting, pressure-overloaded, isolated hearts released the peptide into the coronary effluents, offering the potential for systemic a ctions of AVP from cardiac origin. We conclude that the heart, stressed by acute pressure overload or NO, expresses vasopressin in concentrations suff icient to cause local and potentially systemic effects.