VPT 321: Veterinary Neuropharmacology (2+1)

PATHOPHYSIOLOGICAL ROLE OF ANGIOTENSIN II

Mineralocorticoid secretion

• Angiotensin II is the stimulus for aldosterone secretion from adrenal cortex thereby persistently raise Angiotensin II levels.

Electrolyte and pressure homeostasis

• Renin - angiotensin system sense  decrease tension in the afferent glomerulosa arterioles through intrarenal baroceptor pathway and production of prostaglandins locally.
• Low concentration of sodium ions sensed by macula densa pathway
• Sympathetic outflow response by baroceptor to juxta glomerulus cells is sensed through beta adrenoreceptor pathway.
• In this situation increased renin is translated to angiotensin II causes an acute rise in blood pressure by vasoconstriction and long lasting rise in blood pressure by increasing sodium and water reabsorption in the kidney. 
• Angiotensin II formed within kidney exerts local regulatory effects.

The major pharmacological implications in the mechanism of release of renin are:

• ACE inhibitors and AT₁ antagonists enhance renin release by interfering through feed back mechanism.
• Vasodilators and diuretics stimulate renin release by lowering blood pressure.
• Reduction of sodium ions into macula densa by loop diuretics cause renin release.
• Central sympatholytics and beta blockers decrease renin release.
• NSAIDs inhibit prostaglandin synthesis which in turn decrease renin release.

Develop secondary hyper aldosteronism due to renin angiotensin activation

• CNS - Angiotensin II is formed locally and act as neurotransmitter or neuromodulator by which regulation of thirst, hormone release and sympathetic outflow is mediated.