Diseases that increase the levels of angiotensinogen and the implications thereof:

Diseases that cause an increase in the release or production of corticosteroids, estrogens, thyroid hormones as well as ANG II will lead to an increase in angiotensinogen levels. These types of diseases include hyponatremia, hyperthyroidism as well as heart failure. The increase of angiotensinogen concentration will lead to an increase in the production in ANG II which in turn will lead to hypertension.

Drugs that inhibit the angiotensinogen system by acting on angiotensin receptors have fewer side effects than those that inhibit ACE because of:

ACE plays a role in the degradation of bradykinin. Therefore, if ACE is inhibited there will be an increase in the concentration of bradykinin. Bradykinin have adverse side effects namely cough as well as angioedema. Drugs that inhibits the angiotensinogen system avoids these side effects.

ACE inhibitors have a two-fold mechanism of action in the treatment of hypertension

• A decrease in the degradation of bradykinin leads to an increase in the concentration of bradykinin in the blood. This contributes to the antihypertensive effect.
• Blood pressure as well as vascular resistance is decreased by the blockage of the conversion of ANG I to ANG II by ACE inhibitors.

AT₁ receptors are inhibited by losartan as well as similar drugs. This indirectly stimulate AT₂ receptors through the increase in the concentration of ANG II (caused by the disinhibition of renin release).

Kinins causes a vasodilatory effect in the arteries. This is caused by either a direct inhibition of vascular smooth muscles or by indirectly stimulating the release of Nitric Oxide or vasodilator prostaglandins. However, the effect of kinins on veins is the complete opposite. Kinins in veins causes an inhibition of vascular smooth muscles, or indirectly causes a release of vasoconstrictor prostaglandins. This leads to vasoconstriction in veins.

Receptors that are probably the most involved in the important clinical effects of kinins will be B₂-receptors.

Natriuretic peptides cause an increase in sodium excretion as well as the flow of urine. This leads to a decrease in blood volume. Natriuretic peptides also cause vasodilation and a decrease in arterial blood pressure. All of this will be effective in the treatment of hypertension as well is congestive heart failure.

Neprilysin is a neutral endopeptidase (enzyme) that metabolize natriuretic peptides. The inhibition of this enzyme will lead to an increase in Natriuretic peptides concentration. This will lead to an increase in natriuresis as well as diuresis. This will be effective in the treatment of heart failure. A drug that can be used for this outcome is Sacubitril.

• Endothelium-derived vasodilators: Nitric Oxide
• Endothelium-derived vasoconstrictors:  ET-_B1 receptors