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用普萘洛尔进行长期治疗可增强自发性高血压大鼠主动脉中前列腺素E2和I2的合成。

Chronic treatment with propranolol enhances the synthesis of prostaglandins E2 and I2 by the aorta of spontaneously hypertensive rats.

作者信息

Nishimiya T, Daniell H B, Webb J G, Oatis J, Walle T, Gaffney T E, Halushka P V

机构信息

Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston.

出版信息

J Pharmacol Exp Ther. 1990 Apr;253(1):207-13.

PMID:2109798
Abstract

The effects of treatment with dl, d- or l-propranolol (subcutaneously for 1 week) on arterial blood pressure and on 6-keto prostaglandin (PG) F1 alpha (stable metabolite of PGI2) and PGE2 production by aorta, renal medulla and renal cortex were examined in spontaneously hypertensive rats. dl-Propranolol and l-propranolol significantly (P less than .05) lowered blood pressures from 148 +/- 9/113 +/- 5 (n = 6) and 133 +/- 4/100 +/- 2 (n = 12) mm Hg to 112 +/- 3/80 +/- 3 and 121 +/- 3/81 +/- 3 mm Hg, respectively. Comparable treatment of spontaneously hypertensive rats with inactive d-propranolol was without effect. Basal immunoreactive (i) i6-keto-PGF1 alpha and iPGE2 production by isolated aorta, renal medulla and cortex was not different in vehicle compared to the dl-propranolol-treated rats. In contrast, norepinephrine (1 microM)-stimulated synthesis of i6-keto PGF1 alpha and iPGE2 by the aorta in the dl-propranolol-treated group was significantly (P less than .05) enhanced compared with the vehicle-treated group. Aortic i6-keto-PGF1 alpha and iPGE2 synthesis stimulated by norepinephrine in l-propranolol-treated rats was also significantly (P less than .05) higher than that observed in vehicle and d-propranolol-treated rats. dl-Propranolol treatment did not alter norepinephrine-stimulated renal cortical or medullary i6-keto-PGF1 alpha or iPGE2 synthesis. Indomethacin (5 mg/kg i.p.) given on the last 2 days of dl-propranolol treatment, significantly inhibited aortic i6-keto-PGF1 alpha and iPGE2 production and blunted the antihypertensive effect of dl-propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

在自发性高血压大鼠中,研究了用消旋、右旋或左旋普萘洛尔(皮下注射1周)治疗对动脉血压以及主动脉、肾髓质和肾皮质中6-酮前列腺素(PG)F1α(前列环素I2的稳定代谢产物)和前列腺素E2生成的影响。消旋普萘洛尔和左旋普萘洛尔显著(P<0.05)降低血压,血压分别从148±9/113±5(n = 6)和133±4/100±2(n = 12)mmHg降至112±3/80±3和121±3/81±3 mmHg。用无活性的右旋普萘洛尔对自发性高血压大鼠进行类似治疗则没有效果。与用消旋普萘洛尔治疗的大鼠相比,在溶剂对照中,分离的主动脉、肾髓质和皮质的基础免疫反应性(i)i6-酮-PGF1α和iPGE2生成没有差异。相反,与溶剂对照组相比,在消旋普萘洛尔治疗组中,去甲肾上腺素(1μM)刺激的主动脉i6-酮-PGF1α和iPGE2合成显著(P<0.05)增强。在左旋普萘洛尔治疗的大鼠中,去甲肾上腺素刺激的主动脉i6-酮-PGF1α和iPGE2合成也显著(P<0.05)高于在溶剂对照和右旋普萘洛尔治疗的大鼠中观察到的水平。消旋普萘洛尔治疗未改变去甲肾上腺素刺激的肾皮质或髓质i6-酮-PGF1α或iPGE2合成。在消旋普萘洛尔治疗的最后2天腹腔注射吲哚美辛(5 mg/kg),显著抑制主动脉i6-酮-PGF1α和iPGE2生成,并减弱消旋普萘洛尔的降压作用。(摘要截断于250字)

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