1. The basic biochemical defect of cystic fibrosis (CF) remains undetermined, but impaired function of the β-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 β-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 < 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 β-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.