Key Points
- To determine whether cyclosporine-associated vascular complications arise from increased sympathetic nervous activity or altered vascular reactivity in humans.
- Evaluated 12 patients with rheumatoid arthritis across two sessions: during cyclosporine therapy and while off treatment.
- Assessed dorsal hand vein responsiveness to isoproterenol, prostaglandin E1, phenylephrine, and nitroglycerin using a linear variable differential transformer.
- Quantified total sympathetic activity through whole-body norepinephrine spillover using a radioisotope dilution technique.
- Cyclosporine significantly attenuated vasodilation induced by 60 ng/min isoproterenol (no cyclosporine: 19.8 ± 3.5% vs. cyclosporine: 7.9 ± 2.2%; P = .02).
- Vasodilation induced by prostaglandin E1 was significantly reduced during cyclosporine therapy at both 1000 pg/min (72.6 ± 10.2% vs. 45.6 ± 9.0%) and 2000 pg/min (100.8 ± 14.7% vs. 68.6 ± 8.0%; F = 5.47, P = .047).
- Vascular responses to phenylephrine and nitroglycerin remained unchanged, and norepinephrine spillover showed no significant alteration (no cyclosporine: 516.1 ± 47.9 ng/min vs. cyclosporine: 476.6 ± 51.8 ng/min; P = .42).
Structured PICO
Does cyclosporine alter vascular reactivity or increase sympathetic activity in patients with rheumatoid arthritis?
PPopulation12 patients with rheumatoid arthritis
CComparatorNo cyclosporine (same patients evaluated while not taking the drug)
OOutcomeVascular response in the dorsal hand vein (vasodilation and venoconstriction) and sympathetic activity (norepinephrine spillover)surrogate
Cyclosporine impairs venodilation in response to adenylate cyclase agonists without altering sympathetic activity, suggesting that impaired vasodilation is a primary mechanism for cyclosporine-induced alterations in vascular tone.