• Angiotensin is:
  • A natural hormone that is part of the renin-angiotensin-aldosterone system (RAAS)
  • Stimulated in response to acute, sustained decreases in arterial pressure enhanced sympathetic outflow
  • A direct, potent arteriolar vasoconstrictor (angiotensin II)
  • Responsible for stimulating the adrenal cortex to release aldosterone
• Medications targeting either angiotensin receptors or angiotensin-converting enzymes (ACE) have been developed for the treatment of hypertension (HTN) have major implications for anesthetic management.

• The body has 3 control systems to regulate arterial blood pressure:
  • “Immediate control:” The autonomic nervous system reflexes are capable of minute-to-minute control of blood pressure.
  • “Intermediate control:” Renin angiotensin
  • “Long-term control:” Occurs hours after the decrease in blood pressure by altering the sodium water balance. This process is mediated by aldosterone with the aim of restoring blood pressure to a normal level.
• Renin
  • Synthesized stored in the juxtaglomerular cells in the wall of the renal afferent arterioles
  • Stimulated by a decrease in renal perfusion pressure associated with dehydration, acute hemorrhage, renal artery stenosis, or chronic hyponatremia
  • Converts circulating angiotensinogen to form angiotensin I
• Angiotensinogen is synthesized in the liver released into the plasma.
• Angiotensin I
  • Decapeptide prohormone
  • Not all angiotensin I comes from conversion of angiotensinogen by renin; it is also generated by the vascular endothelium.
• Angiotensin II
  • Octapeptide
  • Not all angiotensin II comes from conversion of angiotensin I by ACE; it is also generated by the vascular endothelium.
  • Plasma half-life is about 50 seconds is cleared rapidly by a variety of enzymes, namely angiotensinases, in the circulation.
  • Has significant physiological activity on the:
    • Cardiovascular system: Angiotensin II binds to angiotensin AT1 receptor (a G protein-coupled receptor) on the vascular smooth muscle, leading to vasoconstriction of the precapillary arterioles postcapillary venules. It is 40 times more potent than norepinephrine, which makes angiotensin II the most powerful endogenous vasoconstrictor. This effect is most profound in the skin, splanchnic vasculature, kidneys, can lead to significant decreases in blood flow to these organs. Coronary artery cerebral artery (to a lesser extent) are also decreased. These pressor responses do not lead to a reflex bradycardia since angiotensin II acts centrally to reset the baroreceptor reflex to a higher pressure. The direct mitogenic effect of angiotensin II on cardiac cells affects cardiac remodeling, may increase myocardial contractility lead to hypertrophy from chronic stimulation.
    • Central nervous system: Angiotensin II acts on the medullary vasomotor center leading to sustained HTN. It can also enhance the release of vasopressin adrenocorticotropic hormone (ACTH) as well as regulate prolactin release in the pituitary gl.
    • Peripheral autonomic nervous system: Angiotensin can stimulate the chromaffin cells in the adrenal medulla to release catecholamines, which is the underlying mechanism for marked HTN associated with pheochromocytoma.
    • Adrenal cortex: Angiotensin can stimulate the synthesis secretion of aldosterone from the adrenal cortex, leading to the retention of sodium excretion of potassium hydrogen in the kidneys.
  • It regulates ovulation hormone production in the ovary hormone production in the testes. It may be partially responsible for preeclamptic symptoms.

• Kidneys: Produce renin
• Liver: Produces angiotensinogen.
• Vascular endothelium: Produces angiotensin (90% of angiotensin I 64% of angiotensin II are generated within endothelium).
• Lungs: Contain the highest concentration of ACE (peptidyl dipeptidase)

• Hypertension: Elevated levels of renin angiotensin lead to increased vascular resistance; this is considered as one of the mechanisms responsible for idiopathic HTN.
• Coronary artery disease: In patients with HTN, the incidence of myocardial infarction was independently associated with the plasma renin activity. The growth effects of angiotensin II may play an important role in the development of coronary artery atherosclerosis peripheral vascular disease.
• Cardiac hypertrophy: Is caused not only by the increased cardiac workload from HTN, but also the mitogenic effect of angiotensin II on the cardiac muscle cells (plays a role in myocardial remodeling).
• Renin-secreting tumors
• Angiotensinogen-secreting tumors

• ACE inhibitors (ACE-I) or angiotensin receptor antagonists/blockers (ARBs) are commonly used drugs in the treatment of HTN, chronic heart failure, or diabetic nephropathy.
  • Heart rate: Minimal effect
  • Contractility: Reflexive increase
  • Cardiac output: Indirect increase
  • Blood pressure: Decrease
  • Systemic pulmonary vascular resistance: Direct decrease
  • Preload: Decrease
  • Renovascular resistance: Decrease
  • Natriuresis: Increase
• Side effects adverse events:
  • Profound prolonged hypotension: The RAAS is responsible for restoring normotension during surgery, especially in a state of hypovolemia decreased vascular resistance. Patients taking ACE inhibitors or angiotensin receptor antagonists preoperatively may develop profound prolonged hypotension from the blockage of this physiologic response during surgery. Whether patients on ACE inhibitors or angiotensin receptor antagonists should discontinue the medication preoperatively remains controversial.
  • Persistent, dry cough angioedema from increased kinins; it appears that there is a decreased incidence with ARBs.
  • Hyperkalemia from decreased aldosterone
  • Exacerbates renal failure in renal artery stenosis, vasoconstricts the efferent arterioles of the glomeruli resulting in an increased glomerular filtration rate (GFR)
  • Angiotensin “escape:” Not all angiotensin arises from the RAAS system. ACE is contained the heart blood vessels where it can exert harmful local effects.
  • Pregnancy: May cause congenital malformations fetal abnormalities
• Benefits: May decrease the degree of vasoconstriction from increased sympathetic tone caused by intraoperative surgical stress; therefore, it may potentially improve perfusion of the vital organs maintain their normal function.

• Hypertension
• ACE Inhibitors Hypotension
• Hypotension
• Chronic Angina

Zhuang-Ting Fang , MD, MSPH