Bradykinin -induced vasodilatation : Role of age, ACE1-inhibitory peptide, mas- and bradykinin receptors

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Siltari , A , Korpela , R & Vapaatalo , H 2016 , ' Bradykinin -induced vasodilatation : Role of age, ACE1-inhibitory peptide, mas- and bradykinin receptors ' , Peptides , vol. 85 , pp. 46-55 . https://doi.org/10.1016/j.peptides.2016.09.001

Title: Bradykinin -induced vasodilatation : Role of age, ACE1-inhibitory peptide, mas- and bradykinin receptors
Author: Siltari, Aino; Korpela, R.; Vapaatalo, H.
Other contributor: University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Riitta Anneli Korpela / Principal Investigator


Date: 2016-11
Language: eng
Number of pages: 10
Belongs to series: Peptides
ISSN: 0196-9781
DOI: https://doi.org/10.1016/j.peptides.2016.09.001
URI: http://hdl.handle.net/10138/229282
Abstract: Bradykinin exerts its vascular actions via two types of receptors, the non-constitutively expressed bradykinin receptor type 1 (BR1) and the constitutive type 2 receptor (BR2). Bradykinin-induced vasorelaxation is age-dependent, a phenomenon related to the varying amounts of BR1 and BR2 in the vasculature. Isoleucine-proline-proline (Ile-Pro-Pro), a bioactive tripeptide, lowers elevated blood pressure and improves impaired endothelium-dependent vasorelaxation in hypertensive rats. It inhibits angiotensin converting enzyme 1 (ACE1). Other mechanisms of action have also been postulated. The aims of the study were to clarify the underlying mechanisms of the age-dependency of bradykinin-induced vasodilatation such as the roles of the two bradykinin receptors, themas-receptor and synergism with Ile-Pro-Pro. The vascular response studies were conducted using mesenteric artery and aorta rings from normotensive 6 wk. (young) and 22 wk. (old) Wistar rats. Cumulative dosing of acetylcholine, bradykinin and angiotensin(1-7) (Ang(1-7))were tested in phenylephrine-induced vasoconstriction with or without 10 min pre-incubation with antagonists against BR1-, BR2- or mas-receptors,Ang(1-7) or ACE1-inhibitors captopril and Ile-Pro-Pro. The bradykinin-induced vasorelaxation in vitro was age-dependent and it was improved by pre incubation with Ile-Pro-Pro, especially in old rats with endothelial dysfunction. The mas-receptor antagonist, D-Pro7-Ang(1-7) abolished bradykinin-induced relaxation totally. Interestingly, BR1 and BR2 antagonists only slightly reduced bradykinin-induced vasorelaxation, as an evidence for the involvement of other mechanisms in addition to receptor activation. In conclusion, bradykinin-induced vasorelaxation was age -dependent and He-Pro-Pro improved it. Mas receptor antagonist abolished relaxation while bradykinin receptor antagonist only slightly reduced it, suggesting that bradykinin-induced vasorelaxation is regulated also by other mechanisms than the classical BR1/BR2 pathway. (C) 2016 Elsevier Inc: All rights reserved.
Subject: Bradykinin
Vasodilatation
Vascular function
Ageing
ACE-inhibition
Bioactive peptides
Ile-Pro-Pro
ANGIOTENSIN-CONVERTING ENZYME
SPONTANEOUSLY HYPERTENSIVE-RATS
CASEIN-DERIVED TRIPEPTIDES
ARACHIDONIC-ACID RELEASE
VAL-PRO-PRO
IN-VITRO
ENDOTHELIAL DYSFUNCTION
BLOOD-PRESSURE
B-2 RECEPTORS
MILK
3111 Biomedicine
317 Pharmacy
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