Venodilation in Raynaud's disease.
The pathogenesis of Raynaud's disease is unclear; an enhanced response to catecholamines has been hypothesised to contribute to this vasospastic disorder. Impaired endothelium-dependent dilation occurs in other diseases associated with vasospasm, such as coronary atherosclerosis. We investigated both endothelium-dependent and endothelium-independent venodilatory function in Raynaud's disease using the hand-vein compliance technique. Full dose-response curves to noradrenaline were constructed in 10 subjects with primary Raynaud's disease and 10 age and sex matched control subjects. The two groups did not have a different response to noradrenaline. Mean (SD) log values of ED50s (the dose producing half maximum response) were 1.00 (0.59) (geometric mean 10 ng/min) in Raynaud's disease compared with 1.29 (0.66) (20 ng/min) in control subjects (p = 0.16). The efficacy of noradrenaline as a venoconstrictor was similar in the two groups: mean maximum dilation (Emax) to noradrenaline was 81 (14)% in the Raynaud's group and 89 (8)% in the control group (p = 0.08). Full dose-response curves to the endothelium-dependent dilator bradykinin were constructed. Emax to bradykinin was significantly lower in the Raynaud's group than in the control group (65 [21] vs 91 [29%], p = 0.02). ED50 values (doses producing half maximum response) for bradykinin were similar in the two groups. Maximum dilation with nitroprusside, a direct releaser of the vasodilator nitric oxide, was not diminished in the Raynaud's group (94 [23] vs 102 [15]% in controls, p = 0.26). These results suggest that endothelium-dependent venodilation is impaired in peripheral vessels in Raynaud's disease, possibly due to diminished release of nitric oxide, and may contribute to the pathogenesis of the disorder.
Bedarida
G
G
Division of Clinical Pharmacology, Stanford University Medical Center, CA 94305-5113.
Kim
D
D
Blaschke
T F
TF
Hoffman
B B
BB
D000804:Angiotensin II / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006225:Hand / Q000098:blood supply*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011928:Raynaud Disease / Q000188:drug therapy / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects*; D014680:Veins / Q000187:drug effects* / Q000503:physiopathology
D000804:Angiotensin II; D009599:Nitroprusside; D001920:Bradykinin; D009638:Norepinephrine