Journal of Literature Pharmacy Sciences

Vascular Functional Effects of the Apelinergic System
Apelinerjik Sistemin Vasküler Fonksiyonel Etkileri
Naciye İŞBİLa, Serdar ŞAHİNTÜRKa, Sadettin DEMİRELa
aDepartment of Physiology, Bursa Uludağ University Faculty of Medicine, Bursa, TURKEY
J Lit Pharm Sci. 2021;10(1):12-20
doi: 10.5336/pharmsci.2020-76153
Article Language: EN
ABSTRACT
The apelinergic system consists of apelin, elabela, and their common receptor apelin receptor (APJ). APJ is a G protein-coupled receptor. Apelin is the first discovered endogenous APJ ligand. Later, elabela was discovered and added to the system. Apelinergic system components have a widespread expression in the human body. The apelinergic system which plays a role in many physiological processes such as body-fluid homeostasis, energy metabolism, and regulation of cardiac contractility participates in the regulation of vascular tone and blood pressure. Apelin and elabela, which have similar effects on vascular tone, differ in their effect mechanisms. APJ is expressed in both vascular endothelial cells and vascular smooth muscle cells. This situation is important because it mediates the opposite effects in vascular tension. Apelin usually has a vasodilator effect through the activation of the endothelial nitric oxide synthase/nitric oxide (NO) pathway in physiological conditions. However, in the absence of a functional endothelium, apelin causes vasoconstriction. Elabela has a vasodilator effect similar to apelin, but it is thought that NO has no role in the vasodilator effect of elabela. When apelin and elabela are administered peripherally, they usually lower blood pressure and exhibit an antihypertensive effect. Therefore, the apelinergic system has great potential to develop alternative agents for the treatment of hypertensive diseases such as essential hypertension and pulmonary hypertension. The half-lives of apelin and elabela are quite short, and current studies have focused on developing longer-acting apelinergic analogs. In this review, we focused on the vascular functional effects and effect mechanisms of the apelinergic system.

Keywords: Apelin; vasodilation; vasoconstriction; hypertension; elabela
ÖZET
Apelinerjik sistem apelin, elabela ve bunların ortak reseptörü apelin reseptörü (APJ)'nden oluşur. APJ, G-proteini kenetli bir reseptördür. Apelin, ilk keşfedilen endojen APJ ligandıdır. Daha sonra ise elabela keşfedilerek sisteme eklenmiştir. Apelinerjik sistem elemanları insan vücudunda yaygın ekspresyona sahiptir. Vücut-sıvı homeostazı, enerji metabolizması ve kardiyak kontraktilitenin düzenlenmesi gibi birçok fizyolojik süreçte rolü olan apelinerjik sistem, damar tonusunun ve kan basıncının düzenlenmesine de katılır. Damar tonusu üzerine benzer etkileri olan apelin ve elabela, etki mekanizmasında farklılık gösterir. APJ, hem damar endotel hücrelerinde hem de damar düz kas hücrelerinde eksprese edilmektedir. Bu durum, damar geriminde karşıt etkilere aracılık etmesi nedeni ile önemlidir. Apelin, fizyolojik koşullarda genellikle endotelyal nitrik oksit sentaz/nitrik oksit (NO) yolağının aktivasyonu aracılığıyla vazodilatatör etki gösterir. Buna karşın apelin, fonksiyonel bir endotelin olmadığı durumlarda vazokonstriksiyona neden olmaktadır. Elabela da apeline benzer şekilde vazodilatatör etki gösterir fakat NO'nun, elabelanın vazodilatatör etkisinde hiçbir rolü olmadığı düşünülmektedir. Apelin ve elabela, periferik olarak uygulandıklarında, genellikle kan basıncını düşürür ve antihipertansif etki gösterirler. Bu nedenle apelinerjik sistem, esansiyel hipertansiyon ve pulmoner hipertansiyon gibi hipertansif hastalıkların tedavisi için alternatif ajanlar geliştirme konusunda büyük bir potansiyele sahiptir. Apelin ve elabelanın yarılanma ömürleri oldukça kısadır ve güncel çalışmalar, daha uzun etkili apelinerjik analoglar geliştirmeye odaklanmıştır. Bu derlemede, apelinerjik sistemin vasküler fonksiyonel etkileri ve etki mekanizmalarına odaklandık.

Anahtar Kelimeler: Apelin; vazodilatasyon; vazokonstriksiyon; hipertansiyon; elabela
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4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com