Ghosh S S, Basu A K, Ghosh S, Hagley R, Kramer L, Schuetz J, Grogan W M, Guzelian P, Watlington C O
Department of Medicine, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298, USA.
Biochem Pharmacol. 1995 Jun 29;50(1):49-54. doi: 10.1016/0006-2952(95)00110-l.
Troleandomycin (TAO), a selective family 3A cytochromes P450 (CYP3A) inhibitor, decreases enhanced in vivo corticosterone 6 beta-hydroxylation and blood pressure in spontaneously hypertensive rats (SHR). Corticosterone 6 beta-hydroxylation was measured in liver and kidney microsomes, to determine ontogeny and the effect of TAO on CYP3A activity at the organ level. SHR kidney CYP3A activity increased from 4 to 8 weeks, stabilized at 11 and 16 weeks, and was much higher than in control (Wistar-Kyoto, WKY) rats at all ages. Hepatic activity showed less consistency in strain difference. TAO produced a relatively large decrease in renal CYP3A activity compared with liver. Although renal CYP3A mRNA was not present in sufficient quantity for detection by northern blot analysis of total RNA, its presence was demonstrated in SHR by reverse transcriptase-polymerase chain reaction amplification. Correlations between renal CYP3A activity and systolic blood pressure in SHR and WKY rats with variations in age, strain and drug treatment are consistent with the role of the enzyme in the pathogenesis of blood pressure elevation in SHR.
三乙酰竹桃霉素（TAO）是一种选择性3A族细胞色素P450（CYP3A）抑制剂，可降低自发性高血压大鼠（SHR）体内增强的皮质酮6β-羟化作用及血压。在肝和肾微粒体中测定皮质酮6β-羟化作用，以确定其个体发生情况以及TAO对器官水平CYP3A活性的影响。SHR肾CYP3A活性在4至8周龄时升高，在11周和16周龄时稳定，且在所有年龄段均远高于对照（Wistar-Kyoto，WKY）大鼠。肝活性在品系差异方面表现出较小的一致性。与肝脏相比，TAO使肾CYP3A活性出现相对较大幅度的降低。尽管通过总RNA的Northern印迹分析无法检测到足够量的肾CYP3A mRNA，但通过逆转录-聚合酶链反应扩增在SHR中证实了其存在。SHR和WKY大鼠中肾CYP3A活性与收缩压随年龄、品系和药物治疗的变化之间的相关性与该酶在SHR血压升高发病机制中的作用一致。
