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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL026320-10
Application #
3338563
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1980-08-01
Project End
1993-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
10
Fiscal Year
1990
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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