The long term objective is to determine the cause of digital vasospasm in patients with Raynaud's phenomenon and develop new therapeutic strategies. Specifically, the role of 5-hydroxytryptamine2 receptors and alpha adrenoceptors will be studied. Plasma and blood (platelets) 52- hydroxytryptamine (5-HT) levels will be measured in normal subjects to determine a normal range and in patients with Raynaud's vasoconstriction and local digital cooling to determine if serotonergic mechanisms are involved. It will be determined if sympathetic nerves can be induced to accumulate 5-HT by 5-HT infusions and release it by tyramine stimulation. Methacholine will be given to patients with Raynaud's phenomenon to demonstrate if the endothelial derived relaxing factor mechanism is intact or if endothelial dysfunction is present. Therapeutic studies will be performed with a combination of an alpha-2 adrenoceptor antagonist (yohimbine) and a serotonergic antagonist (ketanserin). Patients with elevated plasma 5-HT levels will be entered in a study with electrochemical detection. Finger and forearm-hand blood flows are measured venous occlusion plethysmography. Capillary blood flows are measured by the disappearance rate of Na131I from a local injection. In the chronic drug studies, diaries of he frequency, duration, and severity of vasospastic attacks will be kept and finger blood flows measured in a cool room. Raynaud's phenomenon and if combination therapy is of benefit to patients.
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