Circulation: Drugs and Blood Vessels

Question 1

What does more vascular tone mean?

What does less vascular tone mean?

Answer 1

• ↑Vascular tone = ↑Constriction/↓Dilation

- ↓Vascular tone = ↓Constriction/↑Dilation

Question 2

What situations would there need to be an ↑ in vascular tone?

What conditions can cause this drop in blood pressure?

How does ↑vascular tone bring BP back to normal?

Answer 2

↑Vascular tone is done where there’s a large drop in BP! This can be due to:

• Sepsis - systemic infection causing excessive vasodilation = ↓TPR = ↓↓↓BP - poor end organ perfusion
• Anaphylaxis - hypersensitivity reaction causing vasodilation = ↓BP - poor end organ perfusion
• Heart failure - lead to poor CO and BP - poor end organ perfusion
• ↑Vasoconstriction = ↑TPR = ↑BP (BP = CO x TPR)

Question 3

What’s the difference between the actions of Adrenaline and Noradrenaline on most tissues, compared to in skeletal muscle and coronary circulation?

Why is there a difference, in terms of receptor affinity?

Answer 3

Most tissues e.g. GIT, skin:
Adrenaline - Vasoconstriction
Noradrenaline - Vasoconstriction

Skeletal muscle, coronary circulation:
Adrenaline - VASODILATION
Noradrenaline - Vasoconstriction

• Adrenaline has a higher affinity for β than α receptors!
  Noradrenaline has a higher affinity for α than β receptors!

α1-receptors = contraction, β2-receptors = relaxation.

Skeletal muscle and coronary arteries have more β2 than α1-receptors - this is why Adr causes Vasodilation here.

Question 4

What are NA and Adr given to do?

What does NA do when given and in what condition would it be given?

What does Adr do when given and in what condition would it be given?

Answer 4

• Increase BP and flow
• NA is given to act on α1-receptors of VSMCs = ↑TPR = ↑BP. It’s a protective measure as it won’t act on heart - using during Sepsis and Heart failure.
• Adr is given in very high concentrations to have an action on both β1-receptors of heart and α1-receptors of VSMCs = ↑BP. - Epipens used for Anaphylaxis.

Question 5

Why would we want to decrease vascular tone?

What can Hypertension lead to?

What is the role of Vasodilator drugs?

How can they work?

Answer 5

• High BP (HT) is a risk factor for CVS diseases e.g. Angina or Heart failure.
• Endothelium Dysfunction → ↓Tonic vasodilation (via NO) = Poor end organ perfusion + damage. HT also ↑Afterload = Poor CO.
• To PREVENT VASOCONSTRICTION!
• They can block channels, open channels, inhibit certain pathways etc.

Question 6

What are the important pharmacological vasodilator agents?

LOOK AT DIAGRAM!

Answer 6

1. Gq receptor blockers:
   • ARB - block receptors = ↓Vasoconstriction
   • ACEi - ↓Ang II = ↓Vasoconstriction
   • α1 (competitive) and ETA receptor antagonists
2. Ca influx blockers:
   • CCBs (Ca channel blockers) - prevent Ca influx = ↓Vasoconstriction.
   • K channel openers - cause Hyperpolarisation = ↓VGCC = ↓Ca influx = ↓Vasoconstriction
3. Contractile mechanism relaxants:
   • Nitrates (GTN spray) - provide NO = PKG-mediated Vasorelaxation