Responsiveness of superficial hand veins to adrenergic stimuli in patients with cystic fibrosis.
1. The basic biochemical defect of cystic fibrosis (CF) remains undetermined, but impaired function of the beta-adrenoceptor-mediated adenosine 3':5'-cyclic monophosphate (cyclic AMP)-dependent regulatory pathway in secretory cells is likely to be involved in the pathophysiology of the disease. 2. We have compared responsiveness to beta-adrenergic stimulation in vivo by infusing isoprenaline locally into peripheral veins of CF patients and control subjects; the dorsal hand vein technique was used to measure the vascular response to isoprenaline. 3. CF patients required significantly higher doses of isoprenaline for half-maximal dilatation of the preconstricted veins (ED50) than controls (geometric mean: 44.5 ng/min in CF patients compared with 14.8 ng/min in controls; P less than 0.05). Maximal venodilatation was 74 +/- 30% of baseline in CF patients compared with 94 +/- 50% in controls (NS between groups). 4. The clinical score of CF patients was uncorrelated with the ED50 of isoprenaline. Thus the decreased beta-adrenergic responsiveness does not seem to be related to the severity of the disease. 5. Our results indicate a defect in the cyclic-AMP-dependent pathway in vascular smooth muscle cells of CF patients. Whether this is associated with the CF gene defect itself requires further study.
Eichler
H G
HG
Department of Medicine, Stanford University School of Medicine, California.
Eichler
I
I
Lewiston
N
N
Blaschke
T F
TF
Hoffman
B B
BB
D000328:Adult; D003550:Cystic Fibrosis / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006225:Hand / Q000098:blood supply*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014680:Veins / Q000187:drug effects
D010656:Phenylephrine; D007545:Isoproterenol