ABNORMAL DESMOPRESSIN-INDUCED FOREARM VASODILATATION IN PATIENTS WITHHEART-FAILURE - DEPENDENCE ON NITRIC-OXIDE SYNTHASE ACTIVITY

Background: Peripheral vasodilatation in response to muscarinic agonis ts has been shown to be subnormal during heart failure. However, a mor e recent study suggested that the abnormal muscarinic-induced vasodila tation was not due to abnormal nitric oxide synthase activity. This st udy was designed to show that nitric oxide synthase contributes to des mopressin-induced forearm vasodilatation and to determine whether vaso dilatation mediated by nitric oxide synthase is abnormal during heart failure. Methods: Desmopressin (10, 50, and 100 ng/min) was infused in to the brachial artery of 10 healthy subjects and eight patients with heart failure, and forearm blood flow was measured by venous occlusion plethsymography. Desmopressin responses were then recorded during inh ibition of nitric oxide synthase with L-monomethylarginine or after as pirin. Results: In healthy subjects, desmopressin caused a significant (p < 0.001) dose-dependent increase in forearm blood now of 0.9 +/- 0 .6, 4.0 +/- 2.6, and 7.9 +/- 2.6 ml/min/dl, respectively. Desmopressin responses in heart failure of 0.8 +/- 0.6, 1.7 +/- 1.4, and 3.1 +/- 1 .0 ml/min/dl were significantly less (p < 0.001) than normal. L-Monome thylarginine reduced desmopressin responses in normal subjects (p < 0. 01), and this inhibitory effect was significantly (p < 0.01) greater t han in patients with heart failure. Aspirin did not affect desmopressi n-induced vasodilatation. Conclusion: Nitric oxide synthase contribute s to desmopressin-induced forearm vasodilatation. In response to desmo pressin, patients with heart failure have subnormal vasodilatation med iated through nitric oxide synthase.