Abstract 2934: The Effects of Anti-α1-adrenoceptor Autoantibody on Vasoconstriction
Background:Recent studies demonstrated that autoantibody against α1-adrenergic receptor (α1-AR) could be detected in the serum of patients with primary hypertension, and accumulating evidences indicated that the autoantibody possessed agonist-like effects. We hypothesized that anti- α1-AR autoantibody (anti-α1-AA) may affect the blood pressure by contracting vascular smooth muscle and contribute to the development of hypertension.
Methods: The autoantibodies against the second extracellular loop of α1-AR from the sera of the 73 patients with primary hypertension and 86 healthy subjects were detected by ELISA with the synthetic peptide corresponding to the sequence of the second extracellular loop of the human α1-AR adopted as the antigen. IgGs from the anti-α1-AA positive sera of the patients was prepared by affinity chromatography with a MabTrap Kit following the manufacturer’s instructions. The effects of α1-AR on isolated thoracic aortic rings and renal artery of rats in vitro were observed (n=5).
Results: Compared with healthy subjects, the level of anti- α1-AA in primary hypertension were markedly higher than that of healthy subjects as evidenced by the frequency of occurrence (32.3% vs. 3.5%, P<0.01) and the mean geometric titres of the autoantibody (1:80.0±2.74 vs. 1:10.1 ± 1.61, P<0.01). The anti- α1-AA (10 -6mol/L ) increased the tension of isolated thoracic aortic ring from 1.06±0.08g to 1.88±0.06g (P<0.05, vs. control group) and persisted for more than 2 hours, which was similar to the α1-AR agonist, Phenylephrine (10-6mol/L ,from 1.04±0.07g to 2.26±0.03g). The vasoconstriction effects of the antibodies can be blocked by α1-AR antagonist, Prazosin (10 -5mol/L). The tension of isolated renal artery was also increased significantly from 0.25±0.02nN to 3.52±0.04nN (P<0.05, vs. control group) by the antibodies (10-6mol/L), which could be blocked by Prazosin (10-4mol/L).
Conclusions: Our results demonstrated for the first time that the anti- α1-AR autoantibody which exhibited remarkable effects of vascular contraction in vitro and showed no desensitization phenomena may play an important role in both elevating vascular resistance and the development and maintenance of hypertension.