Cardio1- Vascular Control and Drugs

  1. What are the 3 general levels of vascular control and their components?
    • Extrinsic autonomic: baroreceptor reflex
    • Extrinsic hormonal: Epi, Ang II, Vasopressin, Natriuretic peptides
    • Local control: nitric oxide, endothelin, prostaglandins, kinins/histamine
  2. Describe the functions of:
    Nitric oxide
    • NO- vasodilator
    • Endothelin- vasoconstrictor
    • Prostaglandins- vasocontriction and dilation
    • Kinins/histamine- vasodilator
  3. Venoconstriction increases ____________, promotes __________, and pools _______________.
    capillary hydrostatic pressure; tissue/interstitial edema; blood volume away from the heart
  4. How do parallel vascular circuits affect resistance?
    decrease total resistance
  5. The site of greatest pressure drop in circulation.
    across the arterioles
  6. How is reflex vasodilation achieved?
    decrease in tonic vasoconstriction
  7. Describe the affects of the different SNS autonomic receptors in the vasculature. (3)
    • alpha 1 and 2- vasoconstriction
    • beta2- vasodilation
  8. Describe the process of vasoconstriction at the cellular level.
    • 1. NE binds alpha receptor and activates G protein
    • 2. Phospholipase C activated, activating second messenger IP3
    • 3. Ca2+ enters cell via L-type Ca2+ channel
    • 4. Ca2+ binds Ryr receptor on SR, releasing stored Ca2+ from Sr; IP3 also causes more Ca2+ release from SR
    • 5. Ca2+ binds myosin light chain kinase (MLCK)
    • 6. MLCK phosphorylates myosin light chains, allowing them to interact with actin
    • 7. muscle contraction and vasoconstriction
  9. Patients unresponsive to catecholamine infusions (for vasoconstriction) may respond to an infusion of ____________.
  10. __________ is a precursor to NE and is a _________ agonist.
    Dopamine; alpha and beta receptor
  11. ACE is also called __________ and breaks down the vaso________, __________.
    kininase; vasodilator; bradykinin
  12. Nitric oxide is increased by... (3)
    parasympathetic activity, exercise, and by some drugs.
  13. Increased activity of SERCA leads to ___________.
  14. When phospholamban is inhibited, __________ has increased activity and there is ____________.
    SERCA; vasodilation (by increased reuptake of Ca2+ into the SR and less contraction)
  15. Phosphodiesterase (PDE) inhibitors function as ___________ because...
    vasodilators; PDEs break down cAMP and cGMP, which are inhibitors for myocellular contraction
  16. Natriuretic peptides serve as ____________ because...
    vasodilators; they induce renal loss of sodium and water
  17. Causes of hypotension. (8)
    volume depletion (dehydration), cardiac muscle depression (anesthetics), severe bradycardia, severe heart failure [ultimately all cause decreases CO]; excessive vasodilation caused by anesthetics, sepsis, severe acidemia
  18. How does sepsis cause excessive vasodilation?
    causes high levels of NO
  19. How does severe acidemia cause excessive vasodilation?
    alpha-receptors of severely acidemic patients do not respond appropriately to NE
  20. Therapies for hypotension.
    • 1. fluid replacement therapy
    • 2. Drugs: NE, phenylephrine
    • 3. vasopressin (esp. patients with sepsis or acidemia)
  21. What are the most common causes of systemic hypertension in animals? (4)
    • CKD, glomerular disease, Cushing's disease (dogs), hyperthyroidism (cats)
    • [Less common: adrenal tumors secreting Epi or aldosterone]
  22. What are the clinical consequences of systemic hypertension? (4 targets)
    • Brain: cerebral edema, hemorrhagic stroke
    • Eyes: retinal edema and detachment, blindness
    • Heart: LV hypertrophy
    • Kidneys: urinary protein loss, kidney failure
  23. The main longterm therapies for systemic hypertension. (4)
    ACE inhibitors, Ca2+ channel blockers, +/- sodium nitroprusside (IV) or prazosin
  24. How do ACE inhibitors work?
    block kininase (ACE) and inhibit AngI--> AngII (which causes vasoontriction)
  25. Give examples of specific ACE inhibitors. (2)
    ["_____pril"] enalapril, benazepril
  26. How do Ca2+ channel blockers work?
    inhibit Ca2+ entry into vascular smooth muscle, preventing vasoconstriction
  27. Give examples of specific Ca2+ channel blockers? (1)
    ["_____pine"] amlodipine
  28. How does Prazosin work?
    alpha-1 blocker, vasodilation
  29. How does Sodium Nitroprusside work?
    nitrate; increasing nitric oxide--> vasodilation [used as acute therapy for HTN]
  30. What are the effects of beta-receptor agonists, and what are 2 examples of specific drugs?
    vasodilation; dobutamine, isoproterenol
  31. What are examples of specific PDE inhibitor drugs? (2)
    pimobendan, sildenafil
  32. How is nitric oxide produced? Why is this clinically relevant?
    produced by the action of nitric oxide synthase on L-arginine [this AA is sometimes given therapeutically to enhance NO synthesis]
  33. What is thromboxane? What does it cause? What drug reduces it?
    eicosanoid synthesized in platelets; vasoconstriction and clotting; reduced by aspirin
  34. What is prostacyclin? What does it cause? What drug is it reduced by?
    eicosanoid produced by endothelium; vasodilation an inhibits platelets; reduced by aspirin.
  35. How does nitric oxide lead to vasodilation?
    NO signals via guanylate cyclase --> increased cGMP--> inhibition of Ca-MLCK interaction--> decreased contraction--> vasodilation
  36. How does Ach cause vasodilation?
    Ach binds muscarinic receptor--> activated guanylate cyclase--> increased cGMP--> inhibition of Ca-MLCK interaction--> decreased contraction--> vasodilation
  37. Describe the vasodilatory mechanism of cyclic nuecleotides.
    cyclic nucleotides (cAMP and cGMP) inhibit the Ca-MLCK interaction--> less contraction--> vasodilation
  38. How are cyclic nucleotide modulated by drugs to cause vasodilation.
    PDEs degrade cyclic nucleotides, allowing Ca to interact with MLCK and cause vasoconstriction--> PDE inhibitors prevent breakdown of cG/AMP--> vasodilation
  39. Describe the RAAS system.
    renin released in kidney--> cleaves angiotensinogen to AngI--> circulation and gets to pulmonary circulation--> ACE cleaves AngI to AngII--> AngII causes systemic vasoconstriction, cardiac/vascular hypertrophy, thirst/inc plasma volume, renal Na+ and water retention, aldosterone release from adrenal, ADH release from pituitary--> aldosterone and ADH also cause Na+ and water rentention
  40. What are the results of AngII formation from the RAAS system? (6)
    • systemic vasoconstriction
    • cardiac/vascular hypertrophy
    • thirst/increased plasma volume
    • renal Na+ and water retention
    • aldosterone release from adrenal (Na+ and water retention)
    • ADH release from pituitary (water retention, vasoconstriction)
  41. What are triggers for renin release? (3)
    decreased renal blood flow, increase SNS traffic of beta-receptors, decreased Na+ delivery to macula densa
  42. What are triggers for release of vasopressin?
    • Osmotic trigger: dehydration, high serum [Na+]
    • Non-osmotic trigger: low BP sensed by atrial stretch receptors
  43. What are the vascular and renal effects of vasopressin?
    • Vascular: vasoconstriction via V1 receptors 
    • Renal: acts on renal V2 receptors to increase Na+ free water retention and lower serum [Na+]
  44. Give an example of a drug that is a muscarinic agonist and its effects in the vessels.
    Bethanecol- vasodilation
  45. Give an example of a drug that is a muscarinic antagonist and its effects in the vessels.
    Atropine- vasoconstriction, increased HR
  46. Describe the role of cAMP in the heart versus in the vessels.
    • in the heart, cAMP activates PKA, increases Ca2+ release from the SR, and increases contractility
    • in the vessels, cAMP inhibits the interaction b/w MLCK and Ca2+, leading to vasodilation
Card Set
Cardio1- Vascular Control and Drugs
vetmed cardio1