The natural substrate for renin is the plasma protein α2-globulin, which is also known as angiotensinogen. Angiotensinogen is a glycoprotein of 57 kDa that is synthesized and secreted into the bloodstream by the liver. The biosynthesis of angiotensinogen is increased by glucocorticoids, estrogens. The general details of the conversion of angiotensinogen into angiotensin I (a decapeptide) and then into angiotensin II (an octapeptide) are summarized in Figures 1A/B.

Fig1. Fundamentals of blood pressure regulation by integrated actions of the peptide hormones renin, and angiotensin II, and the steroid hormone aldosterone. (A) A flowchart of 14 sequential steps that becomes activated starting with an acute decrease either in blood volume and/or blood pressure that is detected by the kidney, resulting in the release of the enzyme protease, renin, which functions as a hormone. Renin, also known as angiotensinogenase, has 406 amino acids while the functional mature renin has 340 amino acids (~37 kDa). Renin is secreted by the granular cells associated with the glomerulus in response to a drop in blood pressure and/or a decrease in Na+ concentration. Renin’s substrate is the blood protein, α2-globulin (57 kDa), that has been secreted by the liver and then localized within the capillaries of the lungs. This is described in steps #4 to #7 of panel 4A. The hormone angiotensin II is an octapeptide produced by the Angiotensin Converting Enzyme (ACE; step #8) acting on the precursor, angiotensin I. Angiotensin II is a hormone that acts on the zona glomerulosa of the adrenal cortex where it stimulates the production and secretion of the steroid hormone, aldosterone, which binds to its receptor in the kidneys . Then in steps #11 to #14, angiotensin II stimulates the release of the steroid hormone aldosterone from the adrenal cortex (zona glomerulosa) which then binds to its receptor localized in the kidney’s collecting duct where it increases the reabsorption of both Na+ and water and, also, increases secretion of H+ and K+ into the urine, thus leading to an increased blood volume, which increases blood pressure until it has returned to normal. (B) Amino acid sequence of the hormone angiotensin II and two precursor peptides. Panel 4B presents the following: (i) the 13 amino acid pro-hormone portion cleaved off angiotensinogen which has 453 amino acids; (ii) the 10 amino acid peptide sequence of angiotensin I (not a hormone); and (iii) the 8 amino acid peptide sequence of the active hormone, angiotensin II. (C) A schematic illustration of the sources of production of the peptide hormones renin, angiotensin II, and bradykinin and the steroid hormone, aldosterone. There are three important protein sources: (a) the plasma α2-globulin (57 kDa) which is the substrate for (b) the enzyme, renin (42 kDa), that is secreted by the kidney’s juxtaglomerular cells based on changes in renal arterial pressure; and (c) the prekallikrein (86 kDa; see upper right blue rectangle), that is converted by the activated Hagemen Factor (also known as blood coagulation factor XI; 80 kDa) that cleaves off an 85 kDa portion of prekallikrein. When the enzyme kininase II serine protease becomes available, it inactivates bradykinin by removing one or two amino acids from the active bradykinin (a potent vasodilator). The same kininase II enzyme (angiotensin converting enzyme, ACE) also can cleave a 2 amino acid peptide from angiotensin I, which then generates angiotensin II, which is a potent vasoconstrictor. The same angiotensin II, besides being a potent vasoconstrictor, also is a stimulating agent for the biosynthesis of aldosterone in the zona glomerulosa of the adrenal cortex.

In the circulatory system, renin hydrolyzes the Leu–Leu bond of angiotensinogen between residues 10 and 11 to generate the biologically inactive decapeptide angiotensin I. Angiotensin I is then converted by the angiotensinogen converting enzyme (ACE; molecular mass ~200 kDa) that removes the carboxyl-terminal His-Leu dipeptide to yield the octapeptide hormone angiotensin II.

Angiotensin-converting enzyme (ACE) is a zinc-containing protein. Its most important actions are (a) to convert angiotensin I→II and (b) to inactivate bradykinin (a very potent vasodilator). The principal site of con version of angiotensin I to II is in the vascular epithelium of the lung; however ACE activity is also present in the kidney vascular epithelium, heart, brain, and testis. The converting enzyme is also named kininase II because of its action on bradykinin (see Figure 1C.) Angiotensin II, a nonapeptide, is produced by the action of an N-terminal peptidase acting on angiotensin I. Table 1 summarizes the biological actions of the angiotensins. Angiotensin II is the most potent vasoconstrictive agent known. All of the components of the renin–angiotensin system that are necessary to produce angiotensin II are also present in the brain, where the angiotensin II may function as a neurotransmitter.

Table1. Biological Actions of the Angiotensins

There are two principal biological actions of angiotensin II; see Table 1. First it functions as a highly potent vasoconstrictor of the smooth muscle of the blood vessels of the circulatory system where it acts within seconds. This increases the resistance of these arteries for the heart.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم الشؤون الفكريّة يُهدي إصداراته العلمية إلى مكتبات محافظة كركوك

شعبة فاطمة بنت أسد تطلق مسابقتها الإلكترونية (منارة الجود في مهد الصبا) لكتابة القصة للأطفال

المجمع العلمي يقيم برنامجًا قرآنيًا تعليميًا في النجف الأشرف

قسم الشؤون الدينية يقيم مجلسًا عزائيًّا لاستذكار أهل البيت (عليهم السلام)

المزيد

الآخبار الصحية

ما هي أفضل العصائر لصحة القلب وتقوية المناعة والنوم العميق؟

الأطعمة الغنية بالبروتينات النباتية تقلل خطر الأمراض المزمنة

وجع الأوتار قد يخفي خطرا صحيا مرتبطا بالقلب

أزمة "السفينة الموبوءة"..الأرجنتين تحقق في مصدر تفشي "هانتا"

المزيد

الآخبار التكنلوجية

باحثون يحددون تأثير القهوة على الميكروبيوم والمزاج

روسيا.. ابتكار تقنية لمعالجة سبائك التيتانيوم لحماية الطائرات والسيارات

بكين وواشنطن تدرسان إطلاق محادثات رسمية حول الذكاء الاصطناعي

لأول مرة في الولايات المتحدة.. تشغيل مفاعل مصغر نووي يغذي الذكاء الاصطناعي بالطاقة

المزيد

مواضيع ذات صلة

Intragastric Events Leading to Cobalamin Malabsorption

Hormones and Blood Cell Production

Fibroblast Growth Factor-23

Motor Functions of the Intestinal Tract

Control of Renal Magnesium Excretion and Extracellular Magnesium ion Concentration

Regulation of Renal Phosphate Excretion

Control of Calcium Excretion by the Kidneys

Summary of Major Factors That Regulate Potassium Secretion

Overview of Renal Potassium Excretion

Regulation of Internal Potassium Distribution

Production of Steroid Hormones—An Introduction

Profile of Bodily Cholesterol