Our objective is to detect and quantitate differences 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. It is our aim to understand the abnormalities leading to digital artery spasm. Previous work suggests that Raynaud's phenomenon results from an abnormal vasoconstrictor response of digital arteries due to 1) abnormal vascular reactivity; or 2) abnormal neural and humoral stimuli acting on otherwise normal vessels. To this end, vascular reactivity will be studied by determining digital arteriolar opening pressure and segmental arterial systolic pressures to gauge arteriolar and arterial vascular tone as well as the sites of action of drugs and vasomotor responses; capillary blood flow and arteriovenous shunt flow will be measured to determine vascular resistance. Vasoconstrictor responses to (1) the sympathetic nervous system (environmental cooling, mental stress and intra-arterial tyramine); (2) the intra-arterial infusion of norepinephrine and epinephrine (circulating catecholamines); and (3) local digital cooling will be compared in normal subjects and patients. The ability of vasodilators to reverse these vasoconstrictor responses will be studied (isoproterenol, nitroprusside, nitroglycerin, phentolamine, prazosin, histamine, dopamine, nifedipine and acetylcholine). A direct indication of sympathetic nerve activity will be compared in normal subjects and patients by determining the overflow of norepinephrine from sympathetic nerves in the hand during environmental and local cooling, mental stress and drug administration. To determine overflow, the arteriovenous difference of norepinephrine will be determined by high performance liquid chromatography; extraction of norepinephrine by the hand will be determined by a double radioisotopic tracer technique. Functional differences in prejunctional control of sympathetic nerve activity as it affects hand blood flow in normals and patients will be determined by studying effects of alpha- and beta- adrenergic, histaminergic, cholinergic and angiotensin II agonists and antagonists on the overflow of norepinephrine. Since chronic propranolol therapy is associated with peripheral vasospasm, the mechanism by which chronic administration of the drug increases digital and forearm vascular resistance will be studied.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL026320-06
Application #
3338565
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1980-08-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Boston University
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02118
Khan, F; Cohen, R A; Ruderman, N B et al. (1996) Vasodilator responses in the forearm skin of patients with insulin-dependent diabetes mellitus. Vasc Med 1:187-93
Coffman, J D (1994) The diagnosis of Raynaud's phenomenon. Clin Dermatol 12:283-9
Coffman, J D (1994) Effects of endothelium-derived nitric oxide on skin and digital blood flow in humans. Am J Physiol 267:H2087-90
Khan, F; Coffman, J D (1994) Enhanced cholinergic cutaneous vasodilation in Raynaud's phenomenon. Circulation 89:1183-8
Coffman, J D; Cohen, R A (1994) Plasma levels of 5-hydroxytryptamine during sympathetic stimulation and in Raynaud's phenomenon. Clin Sci (Lond) 86:269-73
Khan, F; Palacino, J J; Coffman, J D et al. (1993) Chronic inhibition of nitric oxide production augments skin vasoconstriction in the rabbit ear. J Cardiovasc Pharmacol 22:280-6
Coffman, J D (1992) Alpha-adrenergic and serotonergic receptors and forearm venous compliance in normal human subjects. J Cardiovasc Pharmacol 19:996-9
Coffman, J D (1990) Pathogenesis and treatment of Raynaud's phenomenon. Cardiovasc Drugs Ther 4 Suppl 1:45-51
Coffman, J D; Cohen, R A (1988) Role of alpha-adrenoceptor subtypes mediating sympathetic vasoconstriction in human digits. Eur J Clin Invest 18:309-13
Coffman, J D; Cohen, R A (1988) Serotonergic vasoconstriction in human fingers during reflex sympathetic response to cooling. Am J Physiol 254:H889-93

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