1. 1. How renin–angiotensin pathway regulate blood pressure?
Aside from the capability of the kidneys to control arterial pressure through changes in extracellular fluid volume, the kidneys also have another powerful mechanism for controlling pressure. It is the rennin-angiostenin system. Renin is a protein enzyme released by the kidneys when the arterial pressure falls too low. In turn, it raises the arterial pressure in several ways, thus helping to correct the initial fall in pressure.
2. How renin–angiotensin pathway can be exploited for the discovery & development of cardio vascular drugs?
Renin-angiotensin pathway is exploited for the development of antihypertensive drug by two ways-
a. To antagonize Angiotensin-II
b. To decrease renin release
a.To antagonize Angiotensin-II -
Angiotensin-II is the dominant peptide produced by the renin angiotensin pathway. It is a potent vasoconstrictor that increases total peripheral resistance.
Angiotensin converting enzyme inhibitors decreases the activity of renin-angiotensin pathway. By inhibiting the conversion of angiontensin-II antagonist receptor is required for the development of antihypertensive drug.
b. To decrease renin release –
During hypertension, when the renin-angiontensin pathway becomes over activated increases renin release, thus blood pressure elevated. If renin release can be decreased then the activity of this pathway also decreased. The compound which acts here known as the antihypertensive drug. For this purpose, patient should be given humoral stimulus and use β-blocker.
3. Why most of the ACE Inhibitors are designed as pro drug?
Most of the ACE inhibitors are designed as product because
§ Most of the ACE inhibitors are peptide in nature. So they are polar in nature and can not cross the BBB(Blood Brain Barrier)easily. So they show decreased bioavailability.
For example, Enalaprilate, a ACE inhibitor represent two carboxylate group and the secondary amine, which are responsible for its overall low bioavailability and lipophilicity. To overcome this Enalapril, a prodrug produced from Enalaprilat by esterification shows superior bioavailability.
§ On the other hand, ACE inhibitors are prone to gastric juice. As a result it shows decreased bioavailability in the lower intestine.
For example, amine in enalaprilate is primarily ionized in the small intestine and form a zwiter ion with adjacent carboxylate, which decreases its bioavailability. But in enalapril, amine will be unionized and show more bioavailability.
REGULATIONOF WATER LOSS IN HUMAN BODY
REGULATIONOF WATER LOSS IN HUMAN BODY
