Kost C K, Li P, Williams D S, Jackson E K
Department of Medicine, University of Pittsburgh Medical Center, Pennsylvania 15213-2582, USA.
J Cardiovasc Pharmacol. 1998 Jun;31(6):854-61. doi: 10.1097/00005344-199806000-00008.
It has been postulated that exaggerated renal sensitivity to angiotensin II may be involved in the development and maintenance of hypertension in the spontaneously hypertensive rat (SHR). The purpose of this study was to compare the renal vascular responses to short-term angiotensin II infusions (50 ng/kg/min, i.v.) in conscious SHRs and Wistar-Kyoto (WKY) rats. Renal cortical blood flow was measured in conscious rats by using quantitative renal perfusion imaging by magnetic resonance, and blood pressure was measured by an indwelling carotid catheter attached to a digital blood pressure analyzer. Renal vascular responses to angiotensin II were similar in control SHRs and WKY rats. Pretreatment with captopril to block endogenous production of angiotensin II significantly augmented the renal vascular response to exogenous angiotensin II in the SHRs but not in the WKY rats. The renal vascular responses to angiotensin II were significantly greater in captopril-pretreated SHRs than in WKY rats (cortical blood flow decreased by 1.66 +/- 0.13 ml/min/g cortex in WKY rats compared with 2.15 +/- 0.14 ml/min/g cortex in SHR; cortical vascular resistance increased by 10.5 +/- 1.4 mm Hg/ml/min/g cortex in WKY rats compared with 15.6 +/- 1.7 mm Hg/ml/min/g cortex in SHRs). Responses to angiotensin II were completely blocked in both strains by pretreatment with the angiotensin II AT1-receptor antagonist losartan. Results from this study in conscious rats confirm previous findings in anesthetized rats that (a) the short-term pressor and renal vascular responses to angiotensin II are mediated by the AT1 receptor in both SHRs and WKY rats, and (b) the renal vascular responses to angiotensin II are enhanced in SHRs compared with WKY rats when endogenous production of angiotensin II is inhibited by captopril pretreatment.
据推测，自发性高血压大鼠（SHR）肾脏对血管紧张素II的敏感性过高可能参与了高血压的发生和维持。本研究的目的是比较清醒SHR和Wistar-Kyoto（WKY）大鼠对短期静脉输注血管紧张素II（50ng/kg/min）的肾血管反应。通过磁共振定量肾灌注成像测量清醒大鼠的肾皮质血流量，并用连接数字血压分析仪的留置颈动脉导管测量血压。对照SHR和WKY大鼠对血管紧张素II的肾血管反应相似。用卡托普利预处理以阻断内源性血管紧张素II的产生，可显著增强SHR对外源性血管紧张素II的肾血管反应，但对WKY大鼠无此作用。卡托普利预处理的SHR对血管紧张素II的肾血管反应显著大于WKY大鼠（WKY大鼠皮质血流量减少1.66±0.13ml/min/g皮质，而SHR为2.15±0.14ml/min/g皮质；WKY大鼠皮质血管阻力增加10.5±1.4mmHg/ml/min/g皮质，而SHR为15.6±1.7mmHg/ml/min/g皮质）。用血管紧张素II AT1受体拮抗剂氯沙坦预处理可完全阻断两品系对血管紧张素II的反应。本研究对清醒大鼠的结果证实了先前在麻醉大鼠中的发现，即（a）SHR和WKY大鼠对血管紧张素II的短期升压和肾血管反应均由AT1受体介导，（b）当卡托普利预处理抑制内源性血管紧张素II的产生时，SHR对血管紧张素II的肾血管反应比WKY大鼠增强。
