Entries Tagged 'Renin' ↓

Renin Angiotensin Aldosteron System.

Renin angiotensin aldosteron system.

 

Angiotensinogen (x2 globuten from liver)

Angiotensin1

↓                      (Bradykin)

Inactive peptide

Angiotensin2

↓  Binds with At1

———————————————————————————

↓                                              ↓                                                                           ↓

↓Blood vessel                   Adrenal gland                                                  ↓sympathetic nervous

↓Cuase vasoconstriction                   ↓                                                      ↓catecholamine

↓TPR                               Aldosteron secretion                                        ↓HR

↓BP                                         ↓                                                                          ↓cardiac output

Na+,CT reabsorption                                                   ↓BP

Blood volume

Cardiac output

BP

TPR= Total peripheral resistance

ACE= Angiotensin converting enzyme

BP= Blood pressure.

-         D-2- Methylsucinyl –L- proline had effect similar to SQ20881 but was still only 1/300 as potent the D-isomer, rather than the L-isomer normally sun for amino acid was necessary because of this the isoteric replacement of because NH2 with a CH2 present in suecinyl –L- proline.

-         A comparison of the R2 group of the substrate with the methyl groups of D-2-methyl succinyl –L- proline, illustrate that this methyl group occupies same binding site as the side chain of an L-amino.

-         One of the most important alterations to succinyl-L-proline was the replacement of the succinyl canboxylate with other groups having enhanced affinity for the atom bound to Ace.

-         It produced 3-mercaptopropanoyl-L-proline. This compound has an Ic50 value of 200nm and is more than 1000 times as potent than succinyl-L- proline.

-         Addition of a 2-D-methyl group further enhanced is a competitive inhibitors of Ace with a K1 value of 1.7 nm and was the first ACE inhibitor to be marketed.

-         Systolic dysfunction can be caused by dilated cardiomyopathes, a reduction in muscle mass.

-         Diastolic dysfunction can be cause by increase ventricular stiffness, pericardial disease.

-         Both ventricular hypertrophy and myocardial ischemia can contribute to increased ventricular stiffness.

 

Role Of The Renin-Angiotensin Pathway In Cardiovascular Disorder

Role Of The Renin-Angiotensin Pathway in Cardiovascular disorder.

-         The renin-angiotensin pathway is control to the maintenance of blood volume arterial blood pressure and electrolyte balance.

-         Excessive release of renin , overproduction of angiotensin2 can contribute to variety of cardiovascular disorder. Specifically over activity of this pathway can result in hypertension on or congestive heart failure (CHF)

-         Abnormally high levels of angiotensin2 can contribute to hypertension through both rapid and show pressure response.

-         High level of angiotensin2 can caux cellular hypertrophy as increase both tension. All of these events can cause or exacerbate CHF.

-         The disease results from conditions in which the heart is unable to supply blood at rate sufficient to meet the demands of the body.

-         Similar to hypertension , this pathway physiologic state can occur via a variety of mechanism.

-         Any pathophysiologic event which cause either systolie or diastolic dysfunction with result in CHF

 

Neurogenic signals

Hemodynamic signal ↔ Renin Release ↔ Hormaonal signals

Increased penipheral ↔ Angiotensin2 formation ↔ hypentrophy and remodeling

Regulation or renal function

Slow pressure Response.

Angiotensin Converting Enzyme Inhibitors

Angiotensin converting Enzyme inhibitors:

The Renin-Angiotensin Pathway :  The renin angiotensin system is a complex highly regulated pathway that is integral in the regulation of blood volume. It consists two main enzymes renin and angiotension converting enzyme whose primary purpose is to release angiotensin2 . Angiotensin2 is a potent vasoconstriction .

Asp-Arg-Val-Tyr-His-Pro-Phe-His-lev-Val-He-R

Angiotensinogen Renin

Asp-Arg-Val-Tyr-His-Pro-Phe-lev, angiotensin1

↓  (angiotesin2, converting, enzyme)

Asp-Arg-Val-Tyr-iie-his-pro-phe, angiotensin

↓   (Aminopeptidase)

Arg-Val-Tyr-lle-his-Pro-Phe,

↓(angiotensin3, endo-and, exopeptidase)

Inactive peptidase

Asp-Arg-Val-Tyr-lle-his-pro

Angiotensin1-7

Fig: Schematic representation of the renin-angiotensin pathway. The lahile peptide bonds of angiotensingen and angiotensin1 are high lighted.

Factors Involves In Renin Release

Factors involves in Renin Release:

Rennin release is controlled very closely by

–        Hemodynamic signals

-         Neurogenic signals

-         Hormonal signals

 

-Hemodynamic signals involves the renal juxtaglomerular cell.

-these cell are sensitive to the hemodynamic stretch of the afferent glomerular antenirle .An increased in the stretch implies  a raised blood pressure and results in a reduced release of rennin, while a decrease in the stretch increase rennin secretion.

- these cell are also sensitive to Nacl fuse across the macula densa inhibit rennin release , while decrease in the flux stimulate release.

-Neurogenic enhancement of rennin release occurn via activation of B1- receptors.

- finally , a variety of hormonal signals influence the release or renin. Somatostatin atrial natriuretic factor and angiotensin 2 inhibit renin release , whilevasoactive intestinal poptide. Parathyroid hormone.