Enalapril 7.5mg/5ml oral solution

The renin-angiotensin-aldosterone system (RAAS) is a signaling pathway that works in synergism with the sympathetic system to regulate blood pressure and fluid and electrolyte homeostasis. Activation of this system upon stimulation by different factors, such as low blood pressure and nerve impulses, leads to increased release of norepinephrine (NE) from sympathetic nerve terminals and effects on the vascular growth, vasoconstriction, and salt retention in the kidneys.T28 Renin is released from
Renin acts on the precursor prottein angiotensinogen, which is a plasma globulin synthesized from the liver, to produce cleaved peptide hormone angiotensin I.T28 Angiotensin I then can be further cleaved by ACE to produce angiotensin II, a vasoconstrictive peptide hormone.[label] Present in different isoforms, angiotensin converting enzyme (ACE) is peptidyl dipeptidase enzyme expressed in various tissues, including the vascular tissues, such as the heart, brain, and kidneys.T28 ACE also plays a role in inactivation of bradykinin, a potent vasodepressor peptide.[T28,label] Angiotensin II mediates various actions on the body by working on its G-protein coupled receptors, AT1 and AT2.T28 It causes direct vasoconstriction of precapillary arterioles and postcapillary venules, inhibits the reuptake of NE thereby increasing available levels, stimulates the release of catecholamines from the adrenal medulla, reduces urinary excretion of sodium ions and water by promoting proximal tubular reabsorption, stimulates synthesis and release of aldosterone from the adrenal cortex, and stimulates hypertrophy of both vascular smooth muscle cells and cardiac myocytes.[L6619]

Enalapril is a pharmacologically inactive prodrug that requires hepatic biotransformation to form [enalaprilat], its active metabolite that works on the RAAS to inhibit ACE.[label] Biotransformation is critial for the therapeutic actions of the drug, as enalapril itself is only a weak inhibitor of ACE.[A179131] ACE inhibition results in reduced production and plasma levels of angiotensin II, increased plasma renin activity due to the loss of feedback inhibition by angiotensin II, and decreased aldosterone secretion.[L6586] However, plasma aldosterone levels usually return to normal during long-term administration of enalapril.[A179140] Decreased levels of angiotensin II subsequently leads to the dilatation of peripheral vessles and reduced vascular resistance which in turn lower blood pressure.[A179140] While inhibition of ACE leading to suppression of RAAS is thought to be the primary mechanism of action of enalapril, the drug was shown to still exert antihypertensive effects on individuals with low-renin hypertension. It is suggested that enalapril may mediate its pharmacological actions via other modes of action that are not fully understood.[label] As ACE is structurally similar to kininase I, which is a carboxypeptidase that degrades bradykinin, whether increased levels of bradykinin play a role in the therapeutic effects of enalapril remains to be elucidated.[label]