The effects of autoantibodies against the second extracellular loop of alpha(1)-adrenoceptor on vasoconstriction

Recent studies have demonstrated the presence of autoantibodies against alpha(1)-adrenoceptor (alpha(1)-AAB) in the serum of patients with primary hypertension, and that these autoantibodies exert adrenergic-agonist-like effects. However, their role in the development of hypertension remains unclear. The current study determined whether alpha(1)-AAB can cause vascular contraction, and further investigated the cellular receptors that mediate their vasoactivity. Enzyme-linked immunosorbent assay (ELISA) was used to detect alpha(1)-AAB in blood samples collected from 73 patients with primary hypertension and 86 normotensive patients. IgGs were purified from mixed sera from 25 alpha(1)-AAB-positive hypertensive patients and 20 alpha(1)-AAB-negative normotensives, respectively. The vasoconstrictive effect of purified IgG from the sera of either hypertensive or normotensive patients was observed in isolated rat thoracic aorta, coronary artery, renal artery, middle cerebral artery, and mesenteric artery. The effects of alpha(1)-AAB administration on mean arterial blood pressure in vivo were also assessed. The frequency of alpha(1)-AAB presence was considerably higher in patients with primary hypertension than normotensive subjects (34.2 vs. 10.5%, P < 0.01). In isolated thoracic aortic rings, renal artery, middle cerebral artery, and coronary artery segments, alpha(1)-AAB induced vasoconstriction in a concentration-dependent fashion, which can be completely blocked by prazosin, a selective alpha(1)-adrenoceptor antagonist. The mean arterial pressure significantly increased after the administration of alpha(1)-AAB in vivo. Our results demonstrated that the alpha(1)-AAB (which exhibited remarkable effects of vascular contraction in vitro, elevated blood pressure in vivo, and showed no desensitization phenomena) may play a role in both elevating vascular resistance and the development and maintenance of hypertension.