The long-term objective is to detect and quantitate differnces in the pathophysiologic determinants of digital blood flow amongst normal subjects, patients with idiopathic Raynaud's disease, and patients with Raynaud's phenomenon secondary to scleroderma. The main thrust is to understand the abnormalities leading to digital artery vasospasm.
The specific aim i s to determine the importance of serotonin in the physiological control of digital blood flow in normal subjects and in the vasospasm of digital vessels in patients with Raynaud's phenomenon. Total fingertip blood flow will be measured by venous occlusion, air plethysmography and capillary flow by the disappearance rate of a radioisotope from a local injection in the fingertip. Arteriovenous shunt flow can be estimated by the difference between the two flows. The effect of intra-arterial 5-hydroxytryptamine on finger flow will be determined in normal subjects to assure that the vascular bed reacts to serotonin. The action of a S2-serotonergic receptor antagonist, ketanserin, on finger flow during reflex sympathetic vasoconstriction will be studied in normal subjects and patients with Raynaud's phenomenon to determine if serotonin is causing vasoconstriction. Experiments will be performed with prazosin to prove that alpha-1 adrenoceptors are not being blocked by ketanserin; dose-response curves to ketanserin will be determined to rule out non-specific effects; the blocking action will be studied in subjects vasoconstricted by angiotensin to determine if only sympathetic vasoconstriction is involved; and other vasoconstrictor agents (clonidine, angiotensin) will be given after ketanserin to determine the specificity of the response. The interaction of norepinephrine and serotonin, which has been shown in in vitro studies, will be studied by administering norepinephrine before and during 5HT intra-arterial infusions. Finger flows will be measured in nerve-blocked fingers before and during local cooling with the administration of 5HT and norepinephrine to look for potentiation of vasoconstrictor responses, and before and during ketanserin and nifedipine to determine the mechanism of vasoconstriction due to local cooling. Finally, patients with platelets depleted of serotonin will be studied to search for the source of the serotonin. These studies should determine if serotonin is involved in the normal physiologic control of finger flow during sympathetic stimulation and local cooling and if it might be involved in pathophysiologic digital vasospasm.
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