RENIN (outdated synonym nefrin) — the enzyme belonging to the class of hydrolases and a subclass peptide-hydrolases (KF 126.96.36.199) participates in formation of the substances regulating blood pressure is produced by cells of the juxtaglomerular device of kidneys. Definition of activity of R. in a blood plasma of patients with an idiopathic hypertensia is used as diagnostic and predictive tests.
In 1898 R. A. A. Tigerstedt and P. G. Bergman found out that administration of extract from kidneys of a rabbit caused in experimental animals increase in the ABP, the Substance providing this effect, thermolabile and nedializuyemy, researchers called a renin. Later it was shown that R. does not possess own pressor and vasopressor action.
The river is characterized by high substrate specificity and catalyzes eliminating of decapeptide, i.e. angiotensin I (see. Angiotenzin ), from the N-end of a molecule of angiotensinogen. This reaction is the first in a chain of the enzymatic transformations directed to synthesis of the substances raising blood pressure (see). R.'s participation in this process defines its role in regulation of blood pressure in an organism, and also value for a pathogeny of nek-ry types of hypertensia (see. arterial hypertension ). Angiotensin I does not possess biol. activity, but under the influence of the specific enzyme which is contained in a blood plasma and an endothelium of vessels, peptidildipeptidaza (KF 188.8.131.52) turns into octapeptide — angiotensin II, to-ry possesses powerful angiotonic action.
The river is present at kidneys and a blood plasma of mammals, as well as at other fabrics (a brain, sialadens, a uterus, etc.). Reninopodobny activity is found in nek-ry species of bony fishes (more at fresh-water, than at sea), and also at amphibians and reptiles. The ruble of the person and primacies are catalyzed by splitting of angiotensinogen of other mammals while their R. does not interact with angiotensinogen of the person and primacies.
The river represents a glycoprotein about a pier. it is powerful (weighing) 40 000. The polypeptide chain of R. contains a large number dicarbonic to - t — asparaginic and glutaminic. Isoelectric point (see) The river is in the zone pH 4,5 — 5,7, an optimum pH value for R.'s action — within 5,5 — 7,0. Competitive inhibitors of R. are hemoglobin and alpha and beta chains of a globin. The river is inhibited also by heparin and bile. Inhibitors of serinovy proteinases and metalproteinases — diizopropilftorfosfat, Trasylolum, EDTA do not oppress activity of River. The most powerful inhibitor P. is pepstatin — the N-acetylized pentapeptide emitted from actinomycetes. On its basis the affine sorbents used for allocation and R.'s cleaning from kidneys and a blood plasma of mammals and the person are synthesized.
In a blood plasma and kidneys of the person high-molecular forms P. about a pier are found. weighing 60 000 — 63 000; one of these forms is inactive and is a predecessor R. — a pro-renin. It can pass into an active form at acidulation of solution to pH 3,3 (so-called acid activation), and also at long-term storage at a temperature from +4 to — 5 (so-called cryoactivation) and at action trypsin (see) and kallikrein (see. Kinina ). The last type of activation is, apparently, fizi-ol. mechanism of formation of River. High content of a pro-renin was revealed in a blood plasma of patients with malignant new growths, at a diabetic nephropathy, various hron. diseases of kidneys, after a nephrectomy, and also at pregnancy.
In tissues of mammals the so-called pseudo-renin — enzyme is found, to-ry also chips off angiotensin I from the purified angiotensinogen. However unlike R. the pseudo-renin does not split angiotensinogen in a blood plasma since in it there is an inhibitor of a pseudo-renin. Besides, unlike R. an optimum pH value for action of a pseudo-renin — apprx. 4,5. The pseudo-renin differs from R. on localization in fabrics: the greatest activity of this enzyme is found in a spleen and a thymus gland, and in its blood plasma it is not enough.
Quantitative definition of R. is based on measurement of speed of formation of angiotensin I at R.'s interaction with one of its substrates — the purified angiotensinogen or tetradecapeptide. Angiotensin I is defined by a radio immunological method (see), to-ry differs in high sensitivity and specificity.
Activity and R.'s maintenance in a blood plasma indicate degree of vasoconstriction, to-rogo increase in the ABP, ischemia of body etc. is a consequence. It is established that R. cosecretes especially intensively at change of volume of the circulating liquid. Believe that R.'s activity can serve in blood of patients with an idiopathic hypertensia to one of criteria of a stage and a phase of a disease. Increase in activity of R. in blood is a sign of progressing of a disease. There are data that the labile form of arterial hypertension is characterized by a superactivity of R. in blood while transition of a disease to a stable form is characterized by decrease in its activity in blood. Note that weight of an idiopathic hypertensia and risk of development of its complications increase with increase in activity of R. in blood. Active R.'s definition in a blood plasma is used at diagnosis of renovascular hypertensia for clarification of a possibility of use of a surgical method of treatment of this disease. R.'s definition and potassium in blood along with definition of ions of Na + in urine is applied to differential diagnosis of the idiopathic hypertensia, renovascular hypertensia and hypertensia caused by a tumor of bark of adrenal glands (primary aldosteronism) and the choice of a specific method of treatment — use of antireninovy drugs, diuretics or their combination.
Bibliography: Korolyuk I. P. and Bogdan N. S. Znacheniye of a radio immune method of definition of activity of a renin in a blood plasma for the differentiated therapy of an idiopathic hypertensia, Cardiology, t. 19, No. 10, page 49, 1979; Lara D. A role of reninovy system in developing of a hypertension, in book: Science and mankind, under the editorship of E. B. Etingof, etc., page 35, M., 1980; The renin-angioten-sin system, ed. by J. A. Johnson a. R. R. Anderson, N. Y., 1980; S k e g g s L. T. a. o. The biochemistry of the renin-angiotensin system and its role in hypertension, Amer. J. Med., v. 60, p. 737, 1976, bibliogr.; they, New developments in our knowledge of the chemistry of renin, Fed. Proc. v. 36, p. 1755, 1977; Taylor A. A. Comparative physiology of the renin-angiotensin system, ibid., p. 1776, bibliogr.; Y o k o s a w a • H. a. o. Human renal renin, J. biol. Chem., v. 255, p. 3498, 1980.
L. V. Pavlikhina.