Kost C K, Herzer W A, Li P, Jackson E K
Center for Clinical Pharmacology, University of Pittsburgh Medical Center, Pennsylvania.
J Pharmacol Exp Ther. 1994 Apr;269(1):82-8.
The two aims of the present study were to: 1) explore the hypothesis that the kidneys of spontaneously hypertensive rats (SHR) are more responsive to angiotensin II (Ang II) than are the kidneys of normotensive Wistar Kyoto rats (WKY) and 2) determine whether other vascular beds of SHR exhibit enhanced responsiveness to Ang II, relative to WKY. SHR and WKY received captopril from 4 weeks of age until the time of the experiment to prevent vascular alterations secondary to hypertension. Blood pressure, heart rate, cardiac output and blood flow through the superior mesenteric artery, left renal artery, lower abdominal aorta and right carotid artery were monitored in anesthetized SHR and WKY during acute i.v. administration of Ang II at doses of 0, 3, 10, 30, 100 and 300 ng kg-1 min-1. The heart rate and cardiac output were not significantly affected but the blood pressure was increased to a similar extent in both strains during the Ang II infusion. Hindquarter (aortic) resistance was unaffected by Ang II in both strains. Carotid resistance was slightly increased by the peptide to a similar magnitude in SHR and WKY. The renal and mesenteric vasculature of both strains were highly sensitive to Ang II, with significant dose-related increases in resistance during the infusion. The magnitude of the mesenteric response was not different between SHR and WKY. However, the renal vascular response to Ang II was significantly greater in SHR than in WKY. In conclusion, the enhanced responsiveness to i.v. Ang II occurred selectively in the kidney of SHR and not in the other vessels examined.
1)探讨自发性高血压大鼠(SHR)的肾脏比正常血压的Wistar Kyoto大鼠(WKY)的肾脏对血管紧张素II(Ang II)更敏感这一假说;2)确定相对于WKY,SHR的其他血管床对Ang II是否表现出增强的反应性。SHR和WKY从4周龄开始接受卡托普利治疗,直至实验时,以预防高血压继发的血管改变。在急性静脉注射剂量为0、3、10、30、100和300 ng kg-1 min-1的Ang II期间,监测麻醉状态下的SHR和WKY的血压、心率、心输出量以及通过肠系膜上动脉、左肾动脉、腹主动脉下段和右颈动脉的血流量。心率和心输出量未受到显著影响,但在输注Ang II期间,两种品系的血压均升高到相似程度。两种品系的后肢(主动脉)阻力均不受Ang II影响。该肽使SHR和WKY的颈动脉阻力略有增加,幅度相似。两种品系的肾血管和肠系膜血管对Ang II均高度敏感,在输注期间阻力随剂量显著增加。SHR和WKY之间肠系膜反应的幅度没有差异。然而,SHR对Ang II的肾血管反应明显大于WKY。总之,对静脉注射Ang II的反应性增强选择性地发生在SHR的肾脏,而在所检查的其他血管中未出现。