Iijima F, Malik K U
Department of Pharmacology, College of Medicine, University of Tennessee, Memphis 38163.
Hypertension. 1988 Feb;11(2 Pt 2):I42-6. doi: 10.1161/01.hyp.11.2_pt_2.i42.
Our previous finding that dexamethasone-induced hypertension in rats is associated with enhanced reactivity of mesenteric arteries to arginine vasopressin but not to angiotensin II (Ang II) or norepinephrine has led us to postulate that vasopressin contributes to the development or maintenance of glucocorticoid-induced hypertension. To test this view, we investigated the effects of vasopressin, Ang II, norepinephrine, and the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP on mean arterial blood pressure and heart rate with and without ganglionic blockade with hexamethonium and angiotensin I (Ang I) converting enzyme inhibition with MK 421 in pentobarbital-anesthetized rats made hypertensive by treatment with dexamethasone (1.8 mg/kg/wk for 14 days). Administration of vasopressin, Ang II, or norepinephrine (0.003-3 microgram i.v.) produced a dose-related increase in arterial blood pressure. The pressor response to vasopressin, but not to Ang II or norepinephrine, was greater in dexamethasone-treated than in vehicle-treated animals, and this difference became more pronounced in rats that received hexamethonium and MK 421. Administration of the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP significantly reduced arterial pressure in dexamethasone-treated but not in vehicle-treated animals. Hexamethonium and MK 421 reduced arterial blood pressure in dexamethasone-treated as well as in vehicle-treated rats; however, arterial blood pressure remained higher in the former. Administration of the vasopressin V1 receptor antagonist produced a greater reduction in arterial blood pressure in dexamethasone-treated than in vehicle-treated rats. These data suggest that vasopressin contributes to glucocorticoid-induced hypertension, which is probably due to enhanced vascular reactivity to the peptide.
我们之前的研究发现，地塞米松诱导的大鼠高血压与肠系膜动脉对精氨酸加压素的反应性增强有关，而与对血管紧张素II（Ang II）或去甲肾上腺素的反应性无关。这使我们推测，加压素参与了糖皮质激素诱导的高血压的发生或维持。为了验证这一观点，我们在戊巴比妥麻醉的大鼠中进行了研究，这些大鼠通过地塞米松（1.8mg/kg/周，共14天）处理而患高血压，我们观察了加压素、Ang II、去甲肾上腺素以及加压素V1受体拮抗剂d(CH2)5Tyr(Me)AVP对平均动脉血压和心率的影响，同时观察了使用六甲铵进行神经节阻断以及使用MK 421抑制血管紧张素I（Ang I）转换酶的情况下的影响。静脉注射加压素、Ang II或去甲肾上腺素（0.003 - 3微克）会使动脉血压呈剂量依赖性升高。地塞米松处理的动物对加压素的升压反应比对Ang II或去甲肾上腺素的反应更大，在接受六甲铵和MK 421的大鼠中这种差异更加明显。给予加压素V1受体拮抗剂d(CH2)5Tyr(Me)AVP可显著降低地塞米松处理动物的动脉血压，但对未处理动物无此作用。六甲铵和MK 421可降低地塞米松处理以及未处理大鼠的动脉血压；然而，前者的动脉血压仍然更高。与未处理大鼠相比，给予加压素V1受体拮抗剂后，地塞米松处理的大鼠动脉血压下降幅度更大。这些数据表明，加压素参与了糖皮质激素诱导的高血压，这可能是由于血管对该肽的反应性增强所致。
