Anesthesia Pharmacology:  Vasoactive Peptides

• Sites of Action:  Angiotensin II

  • Vascular smooth muscle

  • Brain

  • Kidney

  • Adrenal cortex

• Renin-angiotensin System Physiology

  • Arterial blood pressure regulation

  • Fluid and electrolyte balance regulation

 

 "Direct renal effects of angiotensin II (not including aldosterone release)"

Boulpaep EL Boron WF Medical Physiology:  a Cellular and Molecular Approach.  St. Louis, Mo:  Elsevier Saunders. p. 771, 2005 "Direct renal effects of angiotensin II (not including aldosterone release." http://en.wikipedia.org/wiki/Angiotensin

• Blood Pressure/Cardiovascular Effects: Angiotensin II

  • Properties:

    • Very potent vasopressor (40 times more potent than norepinephrine).

    • Following IV administration, rapid pressor effect.

    • Vasopressor response: Mechanisms of Action

      • Direct arteriolar smooth muscle contraction.

      • CNS-mediated.

      • ANS-mediated.

    • Minimal reflex bradycardia (angiotensin II CNS action resets baroreceptor reflex system, making it less sensitive).

• Autonomic Effects

  • Stimulates autonomic ganglia

    • Promoting release of epinephrine and norepinephrine.

    • Enhances adrenergic nerve terminal neurotransmission.

      • Iincreases norepinephrine release; reduces norepinephrine re-uptake.

• Slight inotropic cardiac effect

• Adrenal Cortical Effects

  • Angiotensin II:

    • Acts on zona glomerulosa, increasing aldosterone synthesis.

    • At higher doses angiotensin II increases glucocorticoid synthesis.

• Renal Effects

  • Angiotensin II:

    • Renovascular constriction

    • Enhanced sodium reabsorption at proximal tubule

    • Inhibition of renin secretion

• CNS Effects

  • Angiotensin II:

    • Central blood-pressure effects

    • Stimulates drinking (dipsogenic effect)

    • Stimulates vasopressin and ACTH secretion

• Cell Growth Angiotensin II

  • Vascular and cardiac muscle cell mitogen

    • May cause myocardial hypertrophy

    • Angiotensin converting enzyme inhibitors may reduce or prevent morphological changes following myocardial infarction (remodeling), which may lead to cardiac failure (CHF).

Reid, I.A., Vasoactive Peptides, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 287-303.