Liu K L, Aissa A H, Laréal M C, Benzoni D, Vincent M, Sassard J
Department of Physiology and Clinical Pharmacology, URA CNRS 606, Faculty of Pharmacy, Lyon, France.
Hypertension. 1991 Mar;17(3):296-302. doi: 10.1161/01.hyp.17.3.296.
Young, genetically hypertensive Lyon (LH) rats exhibited an increased renal in vivo turnover of norepinephrine and an elevated urinary excretion of thromboxane B2 when compared with normotensive (LN) and low blood pressure (LL) controls. Therefore, the effects of norepinephrine (1.2 x 10(-8) to 9.6 x 10(-7) M) and of phenylephrine (5 x 10(-8) to 1.9 x 10(-6) M) on renal function and the urinary excretion of prostanoids were assessed in isolated perfused kidneys of 8-week-old LH, LN, and LL rats. In addition, the effects of norepinephrine were assessed before and during thromboxane A2/prostaglandin H2 receptor blockade by AH23848 (4 x 10(-6) M). Before drug infusion, LH kidneys differed from those of LN and LL controls by having an elevated renal vascular resistance and a decreased natriuresis and glomerular filtration rate; the urinary output of prostaglandin E2 and F2 alpha, of 6-ketoprostaglandin F1 alpha, and of thromboxane B2 was similar in the three strains. The constrictor effects of norepinephrine and phenylephrine were significantly increased in LH rat kidneys compared with LL but not with LN controls, and their pressure-natriuresis was markedly reduced. Norepinephrine and phenylephrine induced a 10- to 20-fold dose-dependent increase in the synthesis of the four prostanoids, which was more pronounced in LH than in LN and LL rats for thromboxane B2 only. AH23848 infusion significantly reduced the vascular effects of norepinephrine and increased the natriuretic response of LH but not of LN and LL rat kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)
与正常血压（LN）和低血压（LL）对照大鼠相比，年轻的遗传性高血压Lyon（LH）大鼠体内去甲肾上腺素的肾脏周转率增加，血栓素B2的尿排泄量升高。因此，在8周龄的LH、LN和LL大鼠的离体灌注肾脏中，评估了去甲肾上腺素（1.2×10⁻⁸至9.6×10⁻⁷M）和去氧肾上腺素（5×10⁻⁸至1.9×10⁻⁶M）对肾功能和前列腺素尿排泄的影响。此外，在AH23848（4×10⁻⁶M）阻断血栓素A2/前列腺素H2受体之前和期间，评估了去甲肾上腺素的作用。在药物输注前，LH肾脏与LN和LL对照肾脏的不同之处在于肾血管阻力升高、钠利尿和肾小球滤过率降低；三种品系中前列腺素E2、F2α、6-酮前列腺素F1α和血栓素B2的尿量相似。与LL大鼠肾脏相比，LH大鼠肾脏中去甲肾上腺素和去氧肾上腺素的收缩作用显著增强，但与LN对照大鼠相比则不然，并且它们的压力-钠利尿作用明显降低。去甲肾上腺素和去氧肾上腺素诱导四种前列腺素的合成呈10至20倍的剂量依赖性增加，仅血栓素B2在LH大鼠中比在LN和LL大鼠中更明显。输注AH23848显著降低了去甲肾上腺素的血管作用，并增加了LH大鼠肾脏的钠利尿反应，但未增加LN和LL大鼠肾脏的钠利尿反应。（摘要截断于250字）
