title: Hemodynamic and hormonal effects of exogenous adrenomedullin administration in humans and relationship to insulin resistance.
abstract: Although adrenomedullin (AM) is a potent hypotensive peptide that acts mainly as a vasodilative and proliferation inhibitory factor, there have been few hemodynamic studies on AM in humans, especially concerning arterial stiffness and hormonal effects. In addition, AM is a suppressive factor in insulin resistance, suggesting that the effects of AM in a state of insulin resistance are important. To evaluate the effects of AM in humans, 28 participants were intravenously administered AM (5 pmol min(-1) kg(-1)) for 90 min. They also received a representative vasodilator drug, nicardipine, as a reference drug. Blood pressure, heart rate, pulse wave velocity (PWV) and blood flow were monitored throughout the experiment. Hormonal changes were also monitored by blood tests. The effects of AM were compared with those of nicardipine. In addition, the effects of AM were re-evaluated against insulin resistance state. AM and nicardipine produced the same level of hypotension, but AM showed a more potent ability to increase heart rate, blood flow and cardiac output and reduce PWV. AM and nicardipine similarly stimulated plasma noradrenaline and renin activity. However, in the state of insulin resistance, favorable effects of AM on aortic stiffness were blunted and differences between AM and nicardipine disappeared. Furthermore, there was a significant correlation between maximum changes in the PWV induced by AM and the homeostasis model assessment of insulin resistance index (r=0.58, P=0.001). Our results suggest that AM may improve arterial stiffness and act as a compensatory factor against arterial sclerosis. Moreover, decreased reactivity of AM may participate in the progression of arterial sclerosis in insulin resistance.
authors.affiliation: Division of Circulatory and Body Fluid Regulation, Faculty of Medicine, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan. t-kita@po.sphere.ne.jp
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kita
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitamura
mesh_terms: D053607:Adrenomedullin / Q000494:pharmacology*; D000328:Adult; D001158:Arteries / Q000187:drug effects*; D003187:Compliance / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007333:Insulin Resistance; D008875:Middle Aged; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D014665:Vasodilator Agents; D053607:Adrenomedullin