The role of bradykinin and nitric oxide in the cardioprotective action of ACE inhibitors

Hartman, J. Craig

doi:10.1016/0003-4975(95)00192-n

Cited by 77 publications

(49 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this context, several studies investigated the effects of AT1R blockade in myocardial IR, but the results are not consistent across these studies. Losartan or its active metabolite EXP3174 did not reduce IS after myocardial IR in vivo in rabbits (Hartman, 1995), rats (Liu et al, 1996), or dogs (Richard et al, 1993). Moreover, Harada et al (1998) could not prove any IS reduction in AT1a receptor-deficient mice after IR injury.…”

Section: Discussionmentioning

confidence: 85%

Tissue Kallikrein Is Involved in the Cardioprotective Effect of AT1-Receptor Blockade in Acute Myocardial Ischemia

Messadi-Laribi

Griol-Charhbili²,

Pizard³

et al. 2007

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Angiotensin-converting enzyme inhibitors limit infarct size in animal models of myocardial ischemia reperfusion injury. This effect has been shown to be due to inhibition of bradykinin degradation rather than inhibition of angiotensin II formation. The purpose of this study was to determine whether angiotensin AT1 receptor blockade by losartan or its active metabolite EXP3174 protects against myocardial ischemia-reperfusion injury in mice and whether this protection is mediated by the kallikrein kinin system. We subjected anesthetized mice to 30 min of coronary artery occlusion followed by 3 h of reperfusion and evaluated infarct size immediately after reperfusion. Losartan (Los) or EXP3174 [2-n-butyl-4-chloro-1-[(2Ј-(1H-tetrazol-5-yl)biphenyl-4-yI)methyl]imidazole-5-carboxylic acid] were administered 5 min before starting reperfusion at dosages determined by preliminary studies of blood pressure effect and inhibition of angiotensin pressor response. Compared with saline, both drugs significantly reduced myocardial infarct size by roughly 40% (P Ͻ 0.001). Pretreatment of mice with the selective AT2 receptor antagonist PD123,319 [S-(ϩ)-1-([4-(dimethylamino)-3-methylphenyl]methyl)-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo(4,5-c)pyridine-6-carboxylic acid] did not affect infarct size in the absence of losartan but abolished the reduction in infarct size provided by losartan. In tissue kallikrein gene-deficient mice (TK Ϫ/Ϫ ), losartan no longer reduced infarct size. Pretreatment of wild-type mice with the B 2 receptor antagonist icatibant reproduced the effect of TK deficiency. We conclude that AT1 receptor blockade provides cardioprotection against myocardial ischemia-reperfusion injury through stimulation of AT2 receptors. Kallikrein and B 2 receptor are major determinants of this cardioprotective effect of losartan. Our results support the hypothesis of a coupling between AT2 receptors and kallikrein during AT1 receptor blockade, which plays a major role in cardioprotection.

show abstract

Section: Discussionmentioning

confidence: 85%

Tissue Kallikrein Is Involved in the Cardioprotective Effect of AT1-Receptor Blockade in Acute Myocardial Ischemia

Messadi-Laribi

Griol-Charhbili²,

Pizard³

et al. 2007

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…Earlier work on effects of ACE inhibitors in different models of experimental MI has reported similar cardioprotective effects. 16,[27][28][29][30] Among these studies, Hartman 30 attributed the cardioprotective effects of ACE inhibition to bradykinin and nitric oxide involvement, which was further demonstrated by abolition of cardioprotection when animals were pretreated with the bradykinin antagonist, HOE 140, and nitric oxide synthesis was inhibited with NG-nitro-L-arginine methylester. Other clinical and experimental studies have also reported that the beneficial effects of ACE inhibitors were mediated by a bradykinin-nitric oxide pathway.…”

Section: Discussionmentioning

confidence: 99%

Cardioprotective effects of benazepril, an angiotensin-converting enzyme inhibitor, in an ischaemia-reperfusion model of myocardial infarction in rats

Sahoo

Arora

Goyal

et al. 2009

J Renin Angiotensin Aldosterone Syst

View full text Add to dashboard Cite

Introduction. The present study evaluated the effects of benazepril, an angiotensin-converting enzyme inhibitor on haemodynamic, biochemical, and immunohistochemical (Bax and Bcl-2 protein) indices in ischaemia and reperfusion (IR) injury. Materials and methods. Male Wistar albino rats were divided into three groups and were orally administered saline once daily (IR-sham and IR-control) or benazepril (30 mg/kg/day; IR-benazepril) for 14 days. On the 15 th day, in the IR-control and IR-benazepril groups, rats were subjected to left anterior descending coronary artery occlusion for 45 minutes followed by a one-hour reperfusion. Haemodynamic parameters were recorded and rats were sacrificed; hearts were isolated for biochemical estimation and immunohistochemistry.

show abstract

“…However, ACE inhibitor also increases bradykinin levels via blockage of kininase II (ACE). Hartman (30) reported that the protective effect of ACE inhibitor after myocardial infarction may partially depend on the increased bradykinin-stimulated nitric oxide production in cardiac tissues. Therefore, in this study, the beneficial effect of ACE inhibitor may partially include increase of cardiac bradykinin levels in addition to suppression of the Ang II levels.…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of Angiotensin-Converting Enzyme Inhibition in Adriamycin-Induced Cardiomyopathy in Hamsters

Okumura

Jin

Takai

et al. 2002

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-This study was performed to determine whether angiotensin (Ang) II-forming enzymes, angiotensin converting enzyme (ACE) and chymase might contribute to the development of adriamycininduced cardiomyopathy in hamsters. Hamsters were administered adriamycin (2.0 mg/kg per day, i.p.) three times weekly for 2 weeks. In the ACE inhibitor-treated group, the hamsters received lisinopril (20 mg/kg per day, p.o.) for 2 weeks after the last injection of adriamycin. The 4-week mortality rates of the vehicleand ACE inhibitor-treated hamsters were 44% and 12%, respectively. In comparison to the age-matched hamsters used as the control hamsters, a significant decrease in cardiac function and a significant increase in the ratio of the heart weight to the body weight were observed in the vehicle hamsters. Cardiac ACE activity, but not the chymase activity, in the vehicle hamsters was significantly increased in comparison to that in the control hamsters. In the ACE inhibitor-treated group, the increased ACE activity was reduced significantly, and the cardiac hypertrophy and dysfunction were improved significantly. In adriamycininduced cardiomyopathic hamsters, cardiac ACE activity was increased and ACE inhibition significantly improved cardiac function and survival rate, indicating that cardiac ACE, but not the chymase, plays the pivotal role in the development of the adriamycin-induced cardiomyopathy.

show abstract

The role of bradykinin and nitric oxide in the cardioprotective action of ACE inhibitors

Cited by 77 publications

References 13 publications

Tissue Kallikrein Is Involved in the Cardioprotective Effect of AT1-Receptor Blockade in Acute Myocardial Ischemia

Tissue Kallikrein Is Involved in the Cardioprotective Effect of AT1-Receptor Blockade in Acute Myocardial Ischemia

Cardioprotective effects of benazepril, an angiotensin-converting enzyme inhibitor, in an ischaemia-reperfusion model of myocardial infarction in rats

Beneficial Effects of Angiotensin-Converting Enzyme Inhibition in Adriamycin-Induced Cardiomyopathy in Hamsters

Contact Info

Product

Resources

About