Cardiac and vascular effects of long-term losartan treatment in stroke-prone spontaneously hypertensive rats.
Cardiac and vascular effects of long-term losartan treatment in stroke-prone spontaneously hypertensive rats.
复制标题
长期氯沙坦治疗对易发生中风的自发性高血压大鼠的心脏和血管影响。
作者：
P. Gohlke;W. Linz;B. Schölkens;G. Wiemer;Thomas Unger
在先前对易卒中的自发性高血压大鼠（SHRSP）的研究中，我们证明了早发性、长期的血管紧张素转换酶抑制剂治疗改善了心脏功能和代谢，并增加了主动脉cGMP含量，即使在亚降压剂量下也是如此。这些作用可以通过用艾替班特阻断缓激肽2型（B2）受体来预防。在本研究中，我们研究了长期口服血管紧张素1型（AT 1）受体拮抗剂氯沙坦（30 mg/kg/d）对SHRSP的心脏功能和生化参数以及主动脉cGMP含量的影响。氯沙坦可预防高血压和左心室肥厚的发展。在离体灌注心脏中离体测量的心脏功能得到改善，如左心室压力（22.4%）、分化左心室压力（dP/dtmax）（35.1%）和冠状动脉流量（38%）显著增加所示。释放的细胞内酶乳酸脱氢酶和肌酸激酶和乳酸进入冠状动脉流出物分别减少了46.4%，47.2%和63.6%。在心肌组织中，糖原和富含能量的磷酸盐ATP和磷酸肌酸的浓度分别增加了43.2%，33.1%和42.4%，而乳酸减少了57.0%。主动脉组织cGMP含量增加5倍。我们的研究结果表明，慢性阻断AT 1受体与氯沙坦改善心脏功能和代谢，并增加主动脉cGMP含量在SHRSP的程度类似于以前观察到的长期血管紧张素转换酶抑制剂治疗后的降压剂量。本文讨论了氯沙坦对高血压和心肌肥厚的预防作用以及对非AT 1受体的刺激作用，以解释其对心血管的作用。
In previous studies in stroke-prone spontaneously hypertensive rats (SHRSP), we demonstrated that early-onset, long-term angiotensin-converting enzyme inhibitor treatment improved cardiac function and metabolism and increased aortic cGMP content even at sub-antihypertensive doses. These effects could be prevented by bradykinin type 2 (B2) receptor blockade with icatibant. In the present study, we studied the effects of long-term oral treatment with the angiotensin type 1 (AT1) receptor antagonist losartan (30 mg/kg per day) on functional and biochemical parameters of the heart and on cGMP content in the aorta in SHRSP treated prenatally and subsequently up to the age of 20 weeks. Losartan prevented the development of hypertension and left ventricular hypertrophy. Cardiac function measured ex vivo in isolated perfused hearts was improved, as demonstrated by significant increases in left ventricular pressure (22.4%), differentiated left ventricular pressure (dP/dtmax) (35.1%), and coronary flow (38%). The release of the intracellular enzymes lactate dehydrogenase and creatine kinase and of lactate into the coronary effluent was reduced by 46.4%, 47.2%, and 63.6%, respectively. In myocardial tissue, the concentrations of glycogen and the energy-rich phosphates ATP and creatine phosphate were increased by 43.2%, 33.1%, and 42.4%, respectively, whereas lactate was decreased by 57.0%. The aortic tissue content of cGMP was increased fivefold. Our results demonstrate that chronic blockade of AT1 receptors with losartan improved cardiac function and metabolism and increased aortic cGMP content in SHRSP to an extent similar to that observed previously after long-term angiotensin-converting enzyme inhibitor treatment at a comparably antihypertensive dose. Prevention of hypertension and cardiac hypertrophy as well as stimulation of non-AT1 receptors are discussed to explain the cardiac and vascular actions of losartan.
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影响因子：
8.3
作者：
Liu, YH;Yang, XP;Carretero, OA
通讯作者：
Carretero, OA
血管紧张素受体刺激后，冠状激肽的产生介导一氧化氮的释放。
DOI：
10.1161/01.hyp.26.1.164
发表时间：
1995
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Seyedi,N;Xu,X;Nasjletti,A;Hintze,TH
通讯作者：
Hintze,TH
影响因子：
--
作者：
LOPEZ, JJ;LORELL, BH;TANG, SS
通讯作者：
TANG, SS
影响因子：
20.1
作者：
L. A. Sechi;C. A. Griffin;E. F. Grady;J E Kalinyak;M. Schambelan
通讯作者：
L. A. Sechi;C. A. Griffin;E. F. Grady;J E Kalinyak;M. Schambelan
影响因子：
8.3
作者：
LUSCHER, TF;VANHOUTTE, PM
通讯作者：
VANHOUTTE, PM