The Influence of Blood pH on Peripheral Vascular Tone: Possible Role of Proteases and Vaso-Active Polypeptides

Wilkens, Hans J.; Back, Nathan; Steger, R.; Karn, J.

doi:10.1007/978-1-4684-3201-5_15

Cited by 9 publications

(3 citation statements)

References 19 publications

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“…These results are in line with earlier findings showing an activation of kinin-generating pathways in cardiac ischemic tissue: 1) a decrease in peripheral tissue pH after ischemia activates the kallikrein-kinin system (21), 2) coronary artery ligation increases kinins in anesthetized rats (22), 3) BK is increased in coronary sinus blood after coronary occlusion in dogs (23), 4) coronary artery stenosis and sympathetic stimulation induce kinin release in dogs (24), 5) the plasma kallikrein system is activated during myocardial ischemia in human patients (25), and 6) kinin levels are increased in human patients after myocardial infarction (26). An additional aid in understanding the actions of endogenous kinins is the Brown Norway rat (May/Pfd/f), a kinindeficient animal.…”

supporting

confidence: 93%

Role of Kinins in the Pathophysiology of Myocardial Ischemia: In Vitro and In Vivo Studies

Linz¹,

Wiemer²,

Schölkens³

1996

Diabetes

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In ischemia, the heart generates and releases kinins as mediators that seem to have cardioprotective actions. Kinin-generating pathways are present in the heart. Kininogen, kininogenases, kinins, and B2 kinin receptors can be measured in cardiac tissue. Kinins are released under conditions of ischemia. In anesthetized rats and dogs with coronary artery ligation and in human patients with myocardial infarction, kinin plasma levels are increased. In isolated rat hearts, the outflow of kinins is enhanced during ischemia but markedly attenuated after deendothelialization, pointing to the coronary vascular endothelium as the main possible source. Kinins administered locally exert beneficial cardiac effects. In isolated rat hearts with ischemia-reperfusion injuries, perfusion with bradykinin (BK) reduces the duration and incidence of ventricular fibrillation, improves cardiodynamics, reduces release of cytosolic enzymes, and preserves energy-rich phosphates and glycogen stores. In anesthetized animals, intracoronary BK is followed by comparable beneficial changes and limits infarct size. Inhibition of breakdown of BK and related peptides induces beneficial cardiac effects. Treatment with ACE inhibitors such as ramipril increases cardiac kinin levels and reduces post-ischemic reperfusion injuries in isolated rat hearts and infarct size in anesthetized animals. The importance of an intact endothelium that continuously generates kinins is supported by observations that basal and ramipril-induced release of kinins and PGI2 is markedly reduced after deendothelialization of isolated hearts. Blockade of B2 kinin receptors increases ischemia-induced effects. Endothelial formation of NO and PGI2 by ACE inhibition is prevented by the specific B2 kinin receptor antagonist icatibant. In isolated hearts, ischemia-reperfusion injuries deteriorate with icatibant, which also abolishes the cardioprotective effects of ACE inhibitors and of exogenous BK. Infarct size reduction by ACE inhibitors and by BK in anesthetized animals is reversed by icatibant. Kinins contribute to the cardioprotective effects associated with ischemic preconditioning because preconditioning or BK-induced antiarrhythmic and infarct size-limiting effects are attenuated by icatibant. In conclusion, kinins may act as mediators of endogenous cardioprotective mechanisms. Kinins are generated and released during ischemia, with subsequent formation of PGI2 and NO probably derived mainly from the coronary vascular endothelium. Their cardioprotective profile resembles that of ACE inhibitors.

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supporting

confidence: 93%

Role of Kinins in the Pathophysiology of Myocardial Ischemia: In Vitro and In Vivo Studies

Linz¹,

Wiemer²,

Schölkens³

1996

Diabetes

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“…Increased bradykinin levels during ischaemia were observed by Wilkens et al (1970) who reported that a small fall in cardiac tissue pH, which follows an ischaemic insult, induces an activation of the local kinin system. Hashimoto et al (1977) found an increased concentration of bradykinin in coronary sinus blood after coronary occlusion in the dog.…”

Section: Discussionmentioning

confidence: 95%

Ramiprilat increases bradykinin outflow from isolated hearts of rat

Baumgarten

Linz²,

Kunkel

et al. 1993

British J Pharmacology

142

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To establish that bradykinin is formed in the heart we measured bradykinin in the venous effluent from rat isolated hearts perfused with Krebs-Henseleit buffer. In addition, we examined the effect on bradykinin outflow of the angiotensin converting enzyme (ACE) inhibitor, ramiprilat. From rat isolated normoxic hearts a bradykinin outflow of 0.85 ± 0.1 ng ml-' perfusate g-' wet weight was measured. Perfusion with ramiprilat increased the bradykinin concentration to 2.8 ± 0.3 ng ml-' perfusate g ' wet weight. During ischaemia bradykinin outflow maximally increased 8.2 fold to 7.0 ± 0.5 ng ml-' perfusate g-', and in ramiprilat-perfused hearts 5.8 fold to 16.0 ± 1.8 ng ml-' perfusate g'. In the reperfusion period bradykinin outflow normalized to values measured in the respective pre-ischaemic period.The presents data show that bradykinin is continuously formed in the rat isolated heart. Ischaemia increases bradykinin outflow from the heart. Presumably by inhibiting degradation of kinins, ACE inhibition significantly increased the bradykinin concentration during normoxia, ischaemia and reperfusion.

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“…Lastly, spontaneous acidification of post-infarcted myocardium after captopril long-term therapy can be potentially one of the ways it influence on endocrine system. A body of evidence suggests that even slight fall in pH, independently from vessels dilatation, is responsible for the activation of kinin system [61], which is a well-known ACEIs property [62]. …”

Section: Discussionmentioning

confidence: 99%

Cardiomyopathy development protection after myocardial infarction in rats: Successful competition for major dihydropyridines’ common metabolite against captopril

et al. 2017

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During the last 25 years angiotensin-converting enzyme inhibitors spectacularly conquered the field of cardiovascular diseases therapy. Nevertheless, lack of new studies concerning side effects associated with their chronic administration seems to be rather confusing. In our previous research, we proved that the main furnidipines’ metabolite (M-2) possess multiple cardioprotective actions. Currently, we compared effects of post-infarction long-term oral treatment with M-2 and captopril on hemodynamic parameters and “ischemic cardiomyopathy” development in rats. Myocardial infarction was evoked by permanent left anterior descending coronary artery occlusion for 35 days. Surviving rats were treated with captopril (2 × 25 mg/kg) or M-2 (4 mg/kg) from 6th– 35th day. At 35th day rats’ hearts were tested on working heart setup, where following parameters were measured: heart rate, preload pressure, aortic systolic and diastolic pressures, aortic maximum rise and fall, aortic and coronary flow, myocardial oxygen consumption and oximetry in perfusate. Subsequently, heart tissue specimens were assessed during morphological estimation. Captopril caused significant heart rate increase and markedly diminished preload pressure in comparison to M-2. Both drugs evoked essential aortic pressure increase. Aortic flow was significantly decreased after M-2, whereas captopril increased this parameter in comparison to M-2. Both agents caused marked coronary flow increase. Morphologic examination in captopril revealed cardiomyopathic process in 70% of hearts, whereas in M-2 this value reached 30%. Neovascularization of post-infarcted myocardium was visible only after M-2 therapy. Concluding, M-2 presented itself as more attractive agent in long-term post-infarction treatment by preventing cardiomyopathy development, angiogenesis stimulation and preserving cardiac performance.

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The Influence of Blood pH on Peripheral Vascular Tone: Possible Role of Proteases and Vaso-Active Polypeptides

Cited by 9 publications

References 19 publications

Role of Kinins in the Pathophysiology of Myocardial Ischemia: In Vitro and In Vivo Studies

Role of Kinins in the Pathophysiology of Myocardial Ischemia: In Vitro and In Vivo Studies

Ramiprilat increases bradykinin outflow from isolated hearts of rat

Cardiomyopathy development protection after myocardial infarction in rats: Successful competition for major dihydropyridines’ common metabolite against captopril

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