Potential Renal Protective Benefits of Intra-Operative BNP Infusion During Cardiac Transplantation

Brain natriuretic peptide (BNP) reduces the extent of myocardial infarction. We aimed to determine whether BNP may reduce skeletal muscle mitochondrial dysfunctions and oxidative stress through mitochondrial K(ATP) (mK(ATP)) channel opening after ischemia-reperfusion (IR). Wistar rats were assigned to four groups: sham, 3-h leg ischemia followed by 2-h reperfusion (IR), pretreatment with BNP, and pretreatment with 5-hydroxydecanoic acid, an mK(ATP) channel blocker, before BNP. Mitochondrial respiratory chain complex activities of gastrocnemius muscles were determined using glutamate-malate (V(max)), succinate (V(succ)), and N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride ascorbate (V(TMPD/asc)). Apoptosis (Bax-to-Bcl2 mRNA ratio and caspase-3 activity) and oxidative stress (dihydroethidium staining) were also assessed. Compared with the sham group, IR significantly decreased V(max), reflecting complex I, II, and IV activities (-36%, 3.7 ± 0.3 vs. 5.8 ± 0.2 μmol O(2)·min(-1)·g dry wt(-1), P < 0.01), and V(TMPD/asc), reflecting complex IV activity (-37%, 8.6 ± 0.8 vs. 13.7 ± 0.9 μmol O(2)·min(-1)·g dry wt(-1), P < 0.01). IR increased Bax-to-Bcl2 ratio (+57%, 1.1 ± 0.1 vs. 0.7 ± 0.1, P < 0.05) and oxidative stress (+45%, 9,067 ± 935 vs. 6,249 ± 723 pixels, P > 0.05). BNP pretreatment reduced the above alterations, increasing V(max) (+38%, P < 0.05) and reducing Bax-to-Bcl2 ratio (-55%, P < 0.01) and oxidative stress (-58%, P < 0.01). BNP protection against deleterious IR effects on skeletal muscles was abolished by 5-hydroxydecanoic acid. Caspase-3 activities did not change significantly. Conversely, BNP injected during ischemia failed to protect against muscle injury. In addition to maintaining the activity of mitochondrial respiratory chain complexes and possibly decreasing apoptosis, pretreatment with BNP protects skeletal muscle against IR-induced lesions, most likely by decreasing excessive production of radical oxygen species and opening mK(ATP) channels.

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“…It has been successfully used to decrease cardiac filling pressure and/or increase glomerular filtration rate (13,17,52).…”

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confidence: 99%

Pretreatment with brain natriuretic peptide reduces skeletal muscle mitochondrial dysfunction and oxidative stress after ischemia-reperfusion

Talha

Bouitbir

Charles

et al. 2013

Journal of Applied Physiology

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“…All cases of hypotension were effectively corrected with volume substitution (3,13). Zierer et al (2006) showed augmented hemodynamics, a renal protective effect without increased requirement for pressor agents after BNP infusion during cardiac transplantation (5).…”

Section: Discussionmentioning

confidence: 97%

“…BNP leads to greater renal blood flow which increases the filtration rate. This, in turn, increases natriuresis and diuresis (5,6).…”

Section: Discussionmentioning

confidence: 98%

“…The Cardiac output (CO) and Cardiac Index (CI) increase as a result of the decrease in afterload due to peripheral vasodilation. Urine and sodium excretion is increased due to the improved glomerular filtration rate (5), which results in a lesser need for diuretics (6).…”

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confidence: 99%

“…arrhythmias caused by dobutamine, do not occur (9). Therapeutic applications of BNP in cardiac surgery have not been systematically evaluated and most reports are based on small numbers of patients (5,10,11).…”

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confidence: 99%

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Usefulness of BNP-administration in cardiac surgery: Animal model

Bail

Brüllmann

Geim

et al. 2007

Scandinavian Cardiovascular Journal

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Natriuretic peptides and therapeutic applications

2007

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Since the discovery of atrial natriuretic factor by de Bold et al., there has been tremendous progress in our understanding of the physiologic, diagnostic and therapeutic roles of the natriuretic peptides (NPs) in health and disease. Natriuretic peptides are endogenous hormones that are released by the heart in response to myocardial stretch and overload. Three mammalian NPs have been identified and characterized, including atrial natriuretic peptide (ANP or atrial natriuretic factor), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). In addition, Dendroaspis natriuretic peptide (DNP) has been isolated from the venom of Dendroaspis angusticeps (the green mamba snake), and urodilatin from human urine. These peptides are structurally similar and they consist of a 17-amino-acid core ring and a cysteine bridge. Both ANP and BNP bind to natriuretic peptide receptor A (NPR-A) that are expressed in the heart and other organs. Activation of NPR-A generates an increase in cyclic guanosine monophosphate, which mediates natriuresis, inhibition of renin and aldosterone, as well as vasorelaxant, anti-fibrotic, anti-hypertrophic, and lusitropic effects. The NP system thus serves as an important compensatory mechanism against neurohumoral activation in heart failure. This provides a strong rationale for the use of exogenous NPs in the management of acutely decompensated heart failure. In this article, the therapeutic applications of NPs in the acute heart failure syndromes are reviewed. Emerging therapeutic agents and areas for future research are discussed.

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Potential Renal Protective Benefits of Intra-Operative BNP Infusion During Cardiac Transplantation

Cited by 7 publications

References 18 publications

Pretreatment with brain natriuretic peptide reduces skeletal muscle mitochondrial dysfunction and oxidative stress after ischemia-reperfusion

Pretreatment with brain natriuretic peptide reduces skeletal muscle mitochondrial dysfunction and oxidative stress after ischemia-reperfusion

Usefulness of BNP-administration in cardiac surgery: Animal model

Natriuretic peptides and therapeutic applications

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