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Molecular targets of antihypertensive peptides: understanding the mechanisms of action based on the pathophysiology of hypertension.

Majumder K, Wu J - Int J Mol Sci (2014)

Bottom Line: Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE), are often associated with significant adverse effects.Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention.This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides.

View Article: PubMed Central - PubMed

Affiliation: Department of Agricultural, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, AB T6G 2P5, Canada. kaustav@ualberta.ca.

ABSTRACT
There is growing interest in using functional foods or nutraceuticals for the prevention and treatment of hypertension or high blood pressure. Although numerous preventive and therapeutic pharmacological interventions are available on the market, unfortunately, many patients still suffer from poorly controlled hypertension. Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE), are often associated with significant adverse effects. Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention. Some of these peptides have exhibited potent in vivo antihypertensive activity in both animal models and human clinical trials. This review provides an overview about the complex pathophysiology of hypertension and demonstrates the potential roles of food derived bioactive peptides as viable interventions targeting specific pathways involved in this disease process. This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides.

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Related in: MedlinePlus

Endothelial dysfunction and blood pressure regulation. Angiotensin converting enzyme (ACE) converts angiotensin I (Ang I) to angiotensin II (Ang II), Ang II binds with angiotensin receptor 1 (AT1) on endothelium cells as well as vascular smooth muscle cells, then AT1 receptor increases calcium ion (Ca2+) concentration in vascular smooth muscle cells (VSMC) and exerts vasoconstriction. In endothelium cells activation of AT1 receptor increases the production of bET-1 (big endothelin-1). Endothelin-Converting Enzyme (ECE) converts bET-1 to endothelin-1 (ET-1) and exerts vasoconstriction by activating endothelin A/B receptors (ETA/B) in the VSMC. In contrast, activation of ETB receptor in endothelium cells mediates vasodilatory effects via release of nitric oxide (NO) by activating endothelial nitric oxide synthase (eNOS). ACE also converts Bradykinin (Bk) into inactive peptides. Bk binds with bradykinin receptor (B1/2) and activates eNOS, which converts l-Arginine to l-Citrulline and produces NO. NO exerts vasodilation by activating cyclic guanosine monophosphate (cGMP) by inhibiting the concentration of Ca2+ in VSM. In endothelium cells Ang II produces superoxide (O2−) which scavenges NO and produces peroxynitrite (ONOO−), exerts vasoconstriction effect by limiting the supply of NO to the VSM. Signaling pathways illustrated with solid line arrows are representing vasoconstriction and with compound line arrows are representation vasodilation network. Figure 2 modified from [71].
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ijms-16-00256-f002: Endothelial dysfunction and blood pressure regulation. Angiotensin converting enzyme (ACE) converts angiotensin I (Ang I) to angiotensin II (Ang II), Ang II binds with angiotensin receptor 1 (AT1) on endothelium cells as well as vascular smooth muscle cells, then AT1 receptor increases calcium ion (Ca2+) concentration in vascular smooth muscle cells (VSMC) and exerts vasoconstriction. In endothelium cells activation of AT1 receptor increases the production of bET-1 (big endothelin-1). Endothelin-Converting Enzyme (ECE) converts bET-1 to endothelin-1 (ET-1) and exerts vasoconstriction by activating endothelin A/B receptors (ETA/B) in the VSMC. In contrast, activation of ETB receptor in endothelium cells mediates vasodilatory effects via release of nitric oxide (NO) by activating endothelial nitric oxide synthase (eNOS). ACE also converts Bradykinin (Bk) into inactive peptides. Bk binds with bradykinin receptor (B1/2) and activates eNOS, which converts l-Arginine to l-Citrulline and produces NO. NO exerts vasodilation by activating cyclic guanosine monophosphate (cGMP) by inhibiting the concentration of Ca2+ in VSM. In endothelium cells Ang II produces superoxide (O2−) which scavenges NO and produces peroxynitrite (ONOO−), exerts vasoconstriction effect by limiting the supply of NO to the VSM. Signaling pathways illustrated with solid line arrows are representing vasoconstriction and with compound line arrows are representation vasodilation network. Figure 2 modified from [71].

Mentions: NO initiates and maintains vasodilation through a cascade of biological events after diffusing through cell membrane [59]. NO is generated in endothelial cells by nitric oxide synthase (NOS) in a two-step five-electron oxidation of the terminal guanidine nitrogen of l-arginine, generating l-citrulline as a by-product. Three isoforms of NOS have been characterized: endothelial NOS (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS) [67]. Both eNOS and nNOS are present in the normal vascular endothelium [68,69]. After diffusion from endothelial to vascular smooth muscle cells, NO causes vasodilation [69] primarily by activating soluble guanylyl cyclase (sGC) and increasing intracellular concentration of cyclic guanosine-monophosphate [70] (Figure 2). Acute NOS inhibition results in vasoconstriction and reduction in peripheral blood flow [64]. These hemodynamic alterations are entirely reversible with administration of NO donors, such as glyceryl trinitrate (GTN) or sodium nitroprusside (SNP) [71], suggesting that the continuous presence of NO is required to prevent vasoconstriction. In addition, NO also affects cell metabolism, and inhibits mitochondrial respiration and ATP synthesis [59].


Molecular targets of antihypertensive peptides: understanding the mechanisms of action based on the pathophysiology of hypertension.

Majumder K, Wu J - Int J Mol Sci (2014)

Endothelial dysfunction and blood pressure regulation. Angiotensin converting enzyme (ACE) converts angiotensin I (Ang I) to angiotensin II (Ang II), Ang II binds with angiotensin receptor 1 (AT1) on endothelium cells as well as vascular smooth muscle cells, then AT1 receptor increases calcium ion (Ca2+) concentration in vascular smooth muscle cells (VSMC) and exerts vasoconstriction. In endothelium cells activation of AT1 receptor increases the production of bET-1 (big endothelin-1). Endothelin-Converting Enzyme (ECE) converts bET-1 to endothelin-1 (ET-1) and exerts vasoconstriction by activating endothelin A/B receptors (ETA/B) in the VSMC. In contrast, activation of ETB receptor in endothelium cells mediates vasodilatory effects via release of nitric oxide (NO) by activating endothelial nitric oxide synthase (eNOS). ACE also converts Bradykinin (Bk) into inactive peptides. Bk binds with bradykinin receptor (B1/2) and activates eNOS, which converts l-Arginine to l-Citrulline and produces NO. NO exerts vasodilation by activating cyclic guanosine monophosphate (cGMP) by inhibiting the concentration of Ca2+ in VSM. In endothelium cells Ang II produces superoxide (O2−) which scavenges NO and produces peroxynitrite (ONOO−), exerts vasoconstriction effect by limiting the supply of NO to the VSM. Signaling pathways illustrated with solid line arrows are representing vasoconstriction and with compound line arrows are representation vasodilation network. Figure 2 modified from [71].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307246&req=5

ijms-16-00256-f002: Endothelial dysfunction and blood pressure regulation. Angiotensin converting enzyme (ACE) converts angiotensin I (Ang I) to angiotensin II (Ang II), Ang II binds with angiotensin receptor 1 (AT1) on endothelium cells as well as vascular smooth muscle cells, then AT1 receptor increases calcium ion (Ca2+) concentration in vascular smooth muscle cells (VSMC) and exerts vasoconstriction. In endothelium cells activation of AT1 receptor increases the production of bET-1 (big endothelin-1). Endothelin-Converting Enzyme (ECE) converts bET-1 to endothelin-1 (ET-1) and exerts vasoconstriction by activating endothelin A/B receptors (ETA/B) in the VSMC. In contrast, activation of ETB receptor in endothelium cells mediates vasodilatory effects via release of nitric oxide (NO) by activating endothelial nitric oxide synthase (eNOS). ACE also converts Bradykinin (Bk) into inactive peptides. Bk binds with bradykinin receptor (B1/2) and activates eNOS, which converts l-Arginine to l-Citrulline and produces NO. NO exerts vasodilation by activating cyclic guanosine monophosphate (cGMP) by inhibiting the concentration of Ca2+ in VSM. In endothelium cells Ang II produces superoxide (O2−) which scavenges NO and produces peroxynitrite (ONOO−), exerts vasoconstriction effect by limiting the supply of NO to the VSM. Signaling pathways illustrated with solid line arrows are representing vasoconstriction and with compound line arrows are representation vasodilation network. Figure 2 modified from [71].
Mentions: NO initiates and maintains vasodilation through a cascade of biological events after diffusing through cell membrane [59]. NO is generated in endothelial cells by nitric oxide synthase (NOS) in a two-step five-electron oxidation of the terminal guanidine nitrogen of l-arginine, generating l-citrulline as a by-product. Three isoforms of NOS have been characterized: endothelial NOS (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS) [67]. Both eNOS and nNOS are present in the normal vascular endothelium [68,69]. After diffusion from endothelial to vascular smooth muscle cells, NO causes vasodilation [69] primarily by activating soluble guanylyl cyclase (sGC) and increasing intracellular concentration of cyclic guanosine-monophosphate [70] (Figure 2). Acute NOS inhibition results in vasoconstriction and reduction in peripheral blood flow [64]. These hemodynamic alterations are entirely reversible with administration of NO donors, such as glyceryl trinitrate (GTN) or sodium nitroprusside (SNP) [71], suggesting that the continuous presence of NO is required to prevent vasoconstriction. In addition, NO also affects cell metabolism, and inhibits mitochondrial respiration and ATP synthesis [59].

Bottom Line: Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE), are often associated with significant adverse effects.Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention.This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides.

View Article: PubMed Central - PubMed

Affiliation: Department of Agricultural, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, AB T6G 2P5, Canada. kaustav@ualberta.ca.

ABSTRACT
There is growing interest in using functional foods or nutraceuticals for the prevention and treatment of hypertension or high blood pressure. Although numerous preventive and therapeutic pharmacological interventions are available on the market, unfortunately, many patients still suffer from poorly controlled hypertension. Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE), are often associated with significant adverse effects. Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention. Some of these peptides have exhibited potent in vivo antihypertensive activity in both animal models and human clinical trials. This review provides an overview about the complex pathophysiology of hypertension and demonstrates the potential roles of food derived bioactive peptides as viable interventions targeting specific pathways involved in this disease process. This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides.

Show MeSH
Related in: MedlinePlus