Styś T, Styś A, Paczwa P, Szczepańska-Sadowska E, Lipkowski A W
Department of Clinical and Applied Physiology, Warsaw Medical Academy, Poland.
J Physiol Pharmacol. 1998 Mar;49(1):37-49.
The aim of the study was to compare hemodynamic effects of intravenously (i.v.) applied nitric oxide (NO) donor S-nitroso N-acetyl-DL-Penicillamine (SNAP) in conscious spontaneously hypertensive (SHR) to those observed in normotensive Wistar Kyoto (WKY) rats. The study was performed on 7 SHR and 8 WKY instrumented with polyethylene catheters inserted to the abdominal aorta and vena cava for blood pressure (MAP) and heart rate period (HRp) monitoring, and for i.v. administration of SNAP (0.05, 0.1, 0.2, 0.5, 1.0, 2.0, 5.0, 10.0, 20.0, 40.0 and 75.0 microM/kg of body weight). The following differences were found between SHR and WKY rats: 1) the threshold dose of SNAP, eliciting significant decrease of MAP was markedly higher in SHR (1.0 microM/kg b.w.) than in WKY (0.2 microM/kg b.w.), 2) SHR responded with significantly smaller maximum decreases of MAP to administration of 1.0, 2.0, 5.0 and 10.0 microM/kg b.w. of SNAP and with smaller heart rate acceleration to administration of 10.0, 40.0 and 75.0 microM/kg b.w. of SNAP, 3) in SHR MAP decreased progressively, the greatest decline being observed after administration of the highest dose (75 microM/kg b.w.) of SNAP while in WKY the log dose/delta MAP response curve reached plateau beginning with 2 microM/kg b.w. of SNAP, 4) the slopes and intercepts of the regression lines describing relationship between MAP and HRp after administration of SNAP were significantly different in SHR and WKY rats (P < 0.01). The results indicate that SHR are significantly less sensitive to hypotensive effects of NO generated from moderate doses of SNAP.
本研究的目的是比较静脉注射一氧化氮（NO）供体S-亚硝基-N-乙酰-DL-青霉胺（SNAP）对清醒自发性高血压（SHR）大鼠和正常血压的Wistar Kyoto（WKY）大鼠的血流动力学影响。对7只SHR大鼠和8只WKY大鼠进行了实验，这些大鼠均插入了聚乙烯导管至腹主动脉和腔静脉，用于监测血压（MAP）和心率周期（HRp），并用于静脉注射SNAP（0.05、0.1、0.2、0.5、1.0、2.0、5.0、10.0、20.0、40.0和75.0微摩尔/千克体重）。在SHR大鼠和WKY大鼠之间发现了以下差异：1）引起MAP显著下降的SNAP阈值剂量在SHR大鼠（1.0微摩尔/千克体重）中明显高于WKY大鼠（0.2微摩尔/千克体重）；2）SHR大鼠对1.0、2.0、5.0和10.0微摩尔/千克体重的SNAP给药的MAP最大下降反应明显较小，对10.0、40.0和75.0微摩尔/千克体重的SNAP给药的心率加速反应也较小；3）在SHR大鼠中，MAP逐渐下降，在给予最高剂量（75微摩尔/千克体重）的SNAP后观察到最大降幅，而在WKY大鼠中，从2微摩尔/千克体重的SNAP开始，对数剂量/ΔMAP反应曲线达到平台期；4）在SHR大鼠和WKY大鼠中，描述SNAP给药后MAP与HRp之间关系的回归线的斜率和截距显著不同（P<0.01）。结果表明，SHR大鼠对中等剂量SNAP产生的NO的降压作用明显不敏感。
