Impaired microvascular response to cholinergic stimuli in primary Sjogren's syndrome

Abstract

Objective - Signs of a parasympathetic dysfunction have been revealed in primary Sjogren's syndrome (SS). Its role in the pathogenesis and the clinical picture of the disease is not clear. To investigate the responsiveness of SS patients to a cholinergic agonist, a model was used involving examination of the cutaneous microcirculation. The microvascular response to the administration of carbachol was measured, a muscarinic cholinergic agonist. Methods - Twenty two SS patients and 12 controls were examined. Carbachol and 0.9% saline solution were administered intracutaneously into the forearm skin at two distinct places. Skin blood flow (SBF) in the injected areas was measured continuously before and for 10 minutes after the injections by means of a laser Doppler perfusion monitor. The increase in SBF in response to carbachol (dSBF), reflecting vasodilatation, was calculated by a formula including the baseline and the maximum SBF values after the injections of carbachol and saline solution. Results - The vasodilatation was significantly lower in SS patients than in the controls (mean dSBF: 2.1 (range: 1.0-4.5) versus 3.3 (range: 1.7-7.6), p=0.02). With non-responder patients defined as those in whom a smaller response was observed than in any of the controls, 11 of the 22 SS patients proved to be non-responders to carbachol. Comparisons of demographic, clinical and laboratory characteristics and HLA class II genotypes between responder and non-responder SS patients did not show any significant differences. Conclusions - A diminished or absent response to carbachol indicates a cholinergic dysfunction in SS patients. A disturbance in the neurotransmission at a receptorial or postreceptorial level is hypothesised. Unresponsiveness to cholinergic stimuli may contribute to exocrine insufficiency.