López-Morales Mikahela A, Centeno José M, Jover-Mengual Teresa, Marrachelli Vannina G, Burguete María C, Castelló-Ruiz María, Aliena-Valero Alicia, Alborch Enrique, Torregrosa Germán, Salom Juan B, Miranda Francisco J
Unidad Mixta de Investigación Cerebrovascular (UMIC) Departamento de Fisiología Universidad de Valencia - Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
Unidad Mixta de Investigación Cerebrovascular (UMIC) Departamento de Fisiología Universidad de Valencia - Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
Eur J Pharmacol. 2017 Nov 15;815:64-72. doi: 10.1016/j.ejphar.2017.10.010. Epub 2017 Oct 9.
Atrial natriuretic peptide (ANP) is a vasodilator with significant regional differences and controversial effects in the cerebral circulation, a vascular bed particularly prone to diabetes-induced complications. The present study has investigated how alloxan-induced diabetes modifies the mechanisms involved in the response of the rabbit basilar artery to ANP. ANP (10-10M) relaxed precontracted basilar arteries, with higher potency in diabetic than in control rabbits. In arteries from both groups of animals, endothelium removal reduced ANP-induced relaxations. Inhibition of NO-synthesis attenuated ANP-induced relaxation but this attenuation was lower in diabetic than in control rabbits. In control rabbits, indomethacin displaced to the left the concentration-response curve to ANP, without significantly modifying the E value. In diabetic rabbits, indomethacin significantly enhanced arterial relaxations to ANP. In KCl-depolarised arteries, relaxation to ANP was almost abolished both in control and in diabetic rabbits. Iberiotoxin inhibited relaxations to ANP in both groups of rabbits. Glibenclamide and 4-aminopyridine inhibited the ANP-induced relaxations more in diabetic than in control rabbits. Basilar arteries from diabetic rabbits showed decreased natriuretic peptide receptor C expression and no changes in natriuretic peptide receptor A, large conductance calcium-activated K channels (BK), ATP-sensitive K channels (K) and voltage-sensitive K channels (K) expression. These results suggest that diabetes enhances the sensitivity of the rabbit basilar artery to ANP by mechanisms that at least include reduced expression of natriuretic peptide receptor C, and enhanced activity of K and K channels. Furthermore, diabetes reduces endothelial NO and prostacyclin which mediate arterial relaxation to ANP.
心房利钠肽（ANP）是一种血管舒张剂，在脑循环中具有显著的区域差异和存在争议的作用，脑循环是一个特别容易发生糖尿病诱导并发症的血管床。本研究调查了四氧嘧啶诱导的糖尿病如何改变家兔基底动脉对ANP反应所涉及的机制。ANP（10⁻¹⁰M）使预收缩的基底动脉舒张，在糖尿病家兔中的效力高于对照家兔。在两组动物的动脉中，去除内皮均降低了ANP诱导的舒张。抑制一氧化氮合成减弱了ANP诱导的舒张，但这种减弱在糖尿病家兔中低于对照家兔。在对照家兔中，吲哚美辛使ANP的浓度 - 反应曲线向左移位，而不显著改变E值。在糖尿病家兔中，吲哚美辛显著增强了动脉对ANP的舒张。在氯化钾去极化的动脉中，对照和糖尿病家兔对ANP的舒张几乎都被消除。iberiotoxin抑制两组家兔对ANP的舒张。格列本脲和4 - 氨基吡啶在糖尿病家兔中比对照家兔更能抑制ANP诱导的舒张。糖尿病家兔的基底动脉显示利钠肽受体C表达降低，而利钠肽受体A、大电导钙激活钾通道（BK）、ATP敏感性钾通道（K）和电压敏感性钾通道（K）表达无变化。这些结果表明，糖尿病通过至少包括降低利钠肽受体C表达以及增强K和K通道活性的机制增强了家兔基底动脉对ANP的敏感性。此外，糖尿病减少了介导动脉对ANP舒张的内皮一氧化氮和前列环素。
