Increased levels of angiotensinogen are associated with essential hypertension. Essential hypertension is primary hypertension.

The synthesis of angiotensin is stimulated by glucocorticoids, thyroid hormone, estrogens, and angiotensin II. Therefore, abnormally high levels of the glucocorticoids, thyroid hormone, estrogens, and angiotensin II.

A decreased blood pressure leads to more conversion of angiotensinogen to angiotensin II mediated by renin enzyme. This will thus increase the synthesis of angiotensinogen. 

Angiotensin-converting enzyme (ACE) inhibitors are medications that help relax the veins and arteries to lower blood pressure. ACE inhibitors inhibit the production of angiotensin II, a substance that narrows blood vessels. These inhibitors also prevent the conversion of bradykinin to an inactive metabolite (thus enhancing vasodilation, as bradykinin is a vasodilator).

Side effects of ACE inhibitors may include:

• Dry cough
• Increased potassium levels in the blood (hyperkalaemia)
• Fatigue
• Dizziness from blood pressure going too low
• Headaches
• Loss of taste

Angiotensin II receptor blockers help causes vasodilation lower blood pressure and making it easier for heart to pump blood. Angiotensin is a chemical in the body that narrows blood vessels. This narrowing can increase blood pressure and increase workload on the heart. This narrowing is due to release of aldosterone (A steroid hormone that regulates salt and water in the body, thus influencing blood pressure) which is stimulated by angiotensin II. Aldosterone increases blood pressure by causing retention of water and salt, eventually increasing fluid volume.

Inhibition of the angiotensinogen system by angiotensin receptors is associated with fewer effects as the receptors only influence aldosterone release activity, whereas ACE inhibits affect the activity of angiotensin I (thus, alter the activity of angiotensin II and aldosterone) and bradykinin.   

ACE inhibitors are considered to have a two-fold mechanism of action in treatment of hypertension, as these inhibitors prevent the conversion of:

• Angiotensin I to angiotensin II, thus inhibiting the release of aldosterone. Aldosterone-release inhibition promotes water and salt excretion, decreasing fluid volume and eventually blood pressure.
• Bradykinin to an active metabolite. Bradykinin is a vasodilator which widens the blood vessels allowing easier flow of blood, eventually decreasing blood pressure. 

Losartan is an angiotensin II receptor blocker (ARB) used to treat hypertension. Losartan reversibly and competitively prevents angiotensin II binding to the AT₁ receptor in tissues like vascular smooth muscle and the adrenal gland. Losartan and its active metabolite bind the AT₁ receptor with more affinity than they bind to the AT₂ receptor, thus having a direct effect on the angiotensin II receptors.

Kinins are proteins in the blood that cause inflammation and affect blood pressure (especially low blood pressure). They increase blood flow throughout the body by causing vasodilation, which is widening of the blood vessels. Make it easier for fluids to pass through small blood vessels.

Autacoids are biological factors (molecules) which act like local hormones, have a brief duration, and act near their site of synthesis. Histamine and serotonin (5-hydroxytryptamine) are two important amine autacoids.

Histamine is associated with the relief of joint pain or muscle aches and pains. Histamine acts directly on the blood vessels to dilate arteries and capillaries; this action is mediated by both H 1- and H 2-receptors.

Serotonin is the key hormone that stabilizes our mood, feelings of well-being, and happiness. It enables brain cells and other nervous system cells to communicate with each other. Serotonin also helps with sleeping, eating, and digestion.

Serotonin possesses both vasoconstrictor and vasodilator properties. The constrictor action of the monoamine can be due to:

1. Direct activation of vascular smooth muscle; in most blood vessels, this is mediated by S2-serotonergic receptors.
2. Enhancement of action of other endogenous vasoconstrictors such as catecholamines, angiotensin II and the prostanoids (a family of lipid mediators generated by the action of cyclooxygenase).
3. Release of norepinephrine from adrenergic nerves.

The dilator action of serotonin can be due to:

1. 1. Activation of endothelial cells which release endothelium-derived relaxing factor(s); this response appears to be mediated by S1-serotonergic receptors.
   2. Direct inhibition of vascular smooth muscle.
   3. Inhibition of adrenergic neurotransmission by an action on S1-serotonergic receptors.
   4. Release of other endogenous mediators.

Therefore, the effects are similar.

Kinin B2 receptors

Natriuretic peptides may be regarded as treatment for hypertension as it increases sodium and water excretion and causes vasodilation.

The excretion of sodium(salt) and water decreases fluid volume, in turn decreasing blood pressure, will vasodilation allow for widening of blood vessels which facilities easier flow of blood, eventually reducing blood pressure.

Neprilysin inhibitors are used to treat high blood pressure and heart failure. They work by blocking the action of neprilysin thus preventing the breakdown of natriuretic peptides.

Omapatrilat (including entresto and sacubitril/valsartan) is a neprilysin inhibitor, it decreases metabolism of natriuretic peptides and formation of angiotensin II, thus causing vasodilation and increased sodium and water excretion.

The three most important endothelial-derived substances are: nitric oxide (NO), endothelin (ET-1), and prostacyclin (PGI2). NO and PGI2 act as vasodilators, whereas ET-1 serves as a vasoconstrictor

Drugs which act as endothelium-derived vasodilators.

•  Bosentan, macitentan. Nonselective antagonists of endothelin ETA and ETB receptors.
• Sitaxsentan, ambrisentan.  Selective antagonists for ETA receptors.
• Daglutril. Block formation of endothelins and breakdown of natriuretic peptides.

Endothelium-derived vasoconstrictors (factors that stimulate the release of ET-1).

• Low shear stress
• Adrenalin        
• Thrombine      
• Angiotensin II            
• Vasopressinc
• Endotoxin (LPS)        
• Insuline
• Calcium ions