The Role of Kinins in the Antihypertensive and Cardioprotective Effects of ACE Inhibitors

Bönner, Gerd

doi:10.2165/00003495-199700545-00005

Cited by 17 publications

(14 citation statements)

References 23 publications

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“…Complementary to these results, in mice with a deleted BK B 2 receptor gene, an elevated salt sensitivity and a moderate increase in basal blood pressure were reported [47]. Exogenous BK injected intravenously or intra-arterially can induce an immediate and dose-related dilatation of the vessels, resulting in decreases of total peripheral resistance and systemic blood pressure and an increase in venous pooling and a reduced cardiac preload [48]. In healthy volunteers, intravenous administration of the BK B 2 receptor antagonist HOE 140 dose-dependently inhibited BK-induced vasodilation in the forearm vasculature [49].…”

Section: Hypertensionmentioning

confidence: 62%

The therapeutic potential of bradykinin B2 receptor agonists in the treatment of cardiovascular disease

Heitsch¹

2003

Expert Opinion on Investigational Drugs

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The nonapeptide bradykinin (BK) is a Janus-faced hormone, which exerts pathophysiological as well as pronounced beneficial physiological effects, mainly by stimulation of BK B(2) receptors. In various animal models and in humans it has been shown that the stimulation of BK B(2) receptors is not only implicated in the pathogenesis of inflammation, pain and tissue injury but also in powerful cardioprotective mechanisms. Either exogenous administration of BK or locally increased BK concentrations as a consequence of the inhibition of its metabolic breakdown by angiotensin-converting enzyme inhibitors, reveal the significant contribution of BK in powerful cardioprotective mechanisms. These are mainly triggered by the synthesis and release of the vasorelaxant, anti-hypertrophic and anti-atherosclerotic endothelial mediators nitric oxide, prostaglandins and tissue-type plasminogen activator, by ischaemic preconditioning and by an increase in insulin sensitivity. Consequently, BK B(2) receptor agonists may have important clinical value in the treatment and prevention of various cardiovascular disorders such as hypertension, ischaemic heart disease, left ventricular hypertrophy, ventricular remodelling and congestive heart failure as well as diabetic disorders by mimicking the reported beneficial effects of BK. However, none of the currently known potent and selective peptide and non-peptide agonists of BK B(2) receptors--RMP-7 (lobradamil, Cereport; Alkermes), JMV-1116 (Fournier), FR-190997 (Fujisawa) and FR-191413 (Fujisawa)--have been selected for a clinical assessment in cardiovascular indications. One major challenge of this approach is the still unanswered question of whether there is a sufficient safe therapeutic window between potential cardioprotective and pro-inflammatory effects following BK B(2) receptor agonism.

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Section: Hypertensionmentioning

confidence: 62%

The therapeutic potential of bradykinin B2 receptor agonists in the treatment of cardiovascular disease

Heitsch¹

2003

Expert Opinion on Investigational Drugs

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“…This negative effect of aspirin on peripheral arterial constrictor tone may be due to either a direct deleterious effect of aspirin and/or a counteraction of ACEI efficacy, as both mechanisms involve vasodilator PG [7][8][9]. Indeed, a few authors have demonstrated that aspirin may have a direct negative vascular effect in CHF patients [29,30].…”

Section: Discussionmentioning

confidence: 99%

“…Part of the beneficial effects of ACEI is mediated by their interaction with kinins metabolism [4][5][6]. Bradykinin stimulates nitric oxide (NO) and also vasodilator prostaglandins (PG) synthesis via a cyclooxygenase (COX) pathway [7]. Theoretically, COX inhibitors, including aspirin, may partially counteract the efficacy of ACEI but also directly inhibit endogenous vasodilator PG synthesis and/or enhance the vasoconstrictor potential of endothelin [8][9][10], and so have a deleterious effect in CHF.…”

Section: Introductionmentioning

confidence: 99%

Comparative effect of aspirin and clopidogrel on arterial function in CHF

Meune

Mahé

Solal

et al. 2006

International Journal of Cardiology

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“…20,21 However, only limited information on the role of kinins in the therapeutic effects of ACE inhibition is available in humans. ACE inhibition is reported to increase plasma levels of immunoreactive kinin peptides in humans.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-Converting Enzyme Inhibition Modifies Angiotensin but Not Kinin Peptide Levels in Human Atrial Tissue

1999

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Abstract-Angiotensin-converting enzyme (ACE) converts angiotensin I (Ang I) to angiotensin II (Ang II) and metabolizes bradykinin and kallidin peptides. Decreased Ang II levels and increased kinin peptide levels are implicated in the mediation of the therapeutic effects of ACE inhibition. However, alternative non-ACE pathways of Ang II formation have been proposed to predominate in human heart. We investigated the effects of ACE inhibition on cardiac tissue levels of angiotensin and kinin peptides. High-performance liquid chromatography-based radioimmunoassays were used to measure angiotensin peptides and hydroxylated and nonhydroxylated bradykinin and kallidin peptides in right atrial appendages of subjects who had been prepared for cardiopulmonary bypass. Peptide levels in subjects who received ACE inhibitor therapy were compared with those who did not receive ACE inhibitor therapy. ACE inhibition reduced Ang II levels, which was associated with an 80% reduction in the Ang II/Ang I ratio. ACE inhibition did not modify either bradykinin or kallidin peptide levels or the bradykinin-(1-7)/bradykinin-(1-9) ratio. The 80% reduction in the Ang II/Ang I ratio by ACE inhibition indicated a primary role for ACE in the conversion of Ang I to Ang II in atrial tissue. These data support a role for reduced Ang II levels but do not support a role for increased kinin peptide levels in mediating the direct cardiac effects of ACE inhibition. (Hypertension. 1999;34:171-175.)

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The Role of Kinins in the Antihypertensive and Cardioprotective Effects of ACE Inhibitors

Cited by 17 publications

References 23 publications

The therapeutic potential of bradykinin B2 receptor agonists in the treatment of cardiovascular disease

The therapeutic potential of bradykinin B2 receptor agonists in the treatment of cardiovascular disease

Comparative effect of aspirin and clopidogrel on arterial function in CHF

Angiotensin-Converting Enzyme Inhibition Modifies Angiotensin but Not Kinin Peptide Levels in Human Atrial Tissue

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