Question

Angiotensin II. Describe in detail the physiology of Angiotensin II. Include a detailed description of (1) what it is, (2) where it comes from, and (3) how it is activated. Describe in detail 3 mechanisms that act to activate it (the RAS system) and how and when they operate. Lastly describe each of the physiological effects of AngII and explain how each of these effects contribute to homeostasis. Discuss each separately. Be sure to make clear how each effect contributes to homeostasis.

Answer 1

Angiotensin-II is a hormone which is the most active form angiotensin. Angiotensin-II is formed from Angiotensin-I by the action of enzyme 'angiotensin converting enzyme' which is a carboxypeptidase mainly synthesized and secreted by endothelial cells of blood vessels throughout the body, especially of lungs. Renin acts on angiotensinogen to form angiotensin-I which is physiologically inactive and then it will be converted to angiotensin-II immediately by angiotensin converting enzyme.

Hypovolemia, hypertension, hyponatremia or hemorrhage which results in the former conditions, activates renin-angiotensin system by secreting renin from juxtaglomerular cells. They regulate blood volume and blood pressure. Renin acts on angiotensinogen which is a glycoprotein synthesized in the liver and it converts it into angiotensin-I. This angiotensin-I is activated by angiotensin converting enzyme which is secreted by vascular endothelial cells of pulmonary blood vessels especially to form angiotensin-II, which is a most powerful angiotensin to regulate blood pressure and volume.

The physiological actions of angiotensin-II are divided into peripheral actions and central actions.

Peripheral actions:

i)Most potent vasoconstrictor increasing blood pressure drastically when there is a fall in the same.

ii)Increases synthesis and secretion of aldosterone from adrenal cortex which increases sodium and water reabsorption from kidney that increases blood volume, which is an ultimate goal if RAS.

iii)Increases release of nor-epinephrine from post ganglionic sympathetic neurons and potentiates vasoconstriction resulting in an increase in blood pressure, which is an another ultimate goal of RAS.

iv)It causes contraction of mesangial cells to decrease glomerular filtration, thereby preventing excessive fluid loss and maintaining blood volume.

v)Increases sodium and water reabsorption from proximal convoluted tubule of kidney to increase blood volume.

Central actions:

i)Acts on brain centres to decrease sensitivity of baroreflex and potentiates its pressure effect to moniter pressure fall and regulate it by appropriate mechanisms to maintain homeostasis.

ii)Stimulates thirst centre in brain to increase water intake by acting on circum-ventricular organs and helps in increasing blood volume.

iii)Increases secretion of ADH from posterior pituitary to prevent considerable water loss and increasing blood volume ultimately.

iv)Increases secretion of ACTH from anterior pituitary which acts on adrenal cortex and involves in release of aldosterone which increases sodium and water reabsorption.

The ultimate goal of all these actions is to increase blood volume and blood pressure, thus maintaining homeostasis in conditions of fall in blood pressure, hypovolemic shock, hyponatremia and hemorrhage.