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.