Calcium Channel Blockers Overview

Calcium Channel Blockers (CCBs)

• Affect Blood Pressure through reduction in both Cardiac Output (CO) and Total Peripheral Resistance (TPR).

  • Cardiac Output (CO):

    • CCBs decrease both Stroke Volume (SV) and Heart Rate (HR) resulting in a drop in CO.
    • This is due to CCBs blocking L-Type VGCCs in the heart.
      • L-Type VGCCs are responsible for calcium influx for both contraction (in cardiomyocytes) and depolarization (in nodal cells).
      • Blocking these channels delays depolarization and reduces contractility.

  • Total Peripheral Resistance (TPR):

    • Smooth muscle contraction requires calcium influx through L-Type VGCCs.
    • CCBs block this influx, preventing smooth muscle cells from constricting.
    • This results in vasodilation and reduced TPR.

Action of CCBs

• CCBs block Voltage Gated Calcium Channels (VGCCs) in the heart and smooth muscles.
  • Smooth Muscle: Blocking L-Type VGCCs in smooth muscles results in:
    • Reduced Calcium influx into the cell.
    • Less activation of Calmodulin.
    • Reduced activation of Myosin Light-Chain Kinase (MLCK).
    • Fewer myosin heads binding to actin.
    • Weak power strokes.
    • No constriction.
  • Cardiac Muscle: Blocking L-Type VGCCs in cardiomyocytes and nodal cells results in:
    • Decreased contractility.
    • Reduced depolarization leading to slower heart rate.

CCBs and Aldosterone Secretion

• CCBs can reduce aldosterone synthesis and secretion from the adrenal cortex.
  • Both T-Type and L-Type VGCCs are found in aldosterone-producing cells.
  • Increased intracellular calcium stimulates aldosterone synthesis.
  • By blocking these channels, CCBs reduce intracellular calcium levels, leading to reduced aldosterone secretion.

Effects of Reduced Aldosterone

• Reduced aldosterone production results in lower sodium and water retention, reduced blood volume, and consequently, reduced blood pressure.
  • Also, since aldosterone is a vasoconstrictor, less aldosterone further contributes to vasodilation, lowering blood pressure.

Summary

• CCBs affect blood pressure mainly by reducing cardiac output and total peripheral resistance.
• They achieve this by blocking L-Type VGCCs in cardiac and smooth muscle, reducing contractility and preventing smooth muscle constriction.
• Additionally, they reduce aldosterone production by lowering calcium levels in adrenal cortex cells.
• This further decreases blood pressure by reducing sodium and water retention and decreasing vasoconstriction.

Key Facts:

• CCBs can have negative chronotropic (decrease HR) and negative inotropic (decrease contractility) effects by blocking L-type VGCCs.
• CCBs can be used to treat hypertension, angina, and other cardiovascular conditions.
• Different subtypes of CCBs exist, each with specific effects on different tissues and receptors.
• A new calcium channel blocker binding both T-Type and L-Type channels would have a significant impact on both vasoconstriction and aldosterone production, leading to larger reductions in both TPR and blood pressure.

This quiz covers the effects of Calcium Channel Blockers (CCBs) on blood pressure, including their impact on cardiac output and total peripheral resistance. It discusses how CCBs block L-Type voltage-gated calcium channels in both the heart and smooth muscles leading to reduced heart rate and improved vasodilation.