Angina: The Balance between Myocardial Oxygen Supply and Demand

No pain vs. Angina

O₂ Supply: O₂ Demand:

Aortic diastolic pressure Heart Rate

Duration of diastole Contractility

Coronary vascular bed resistance Wall stress

*when demand exceeds supply, there is angina; when there is plenty of supply to meet the demand, there is no pain.

Drugs will act at a cellular level, so we must understand how smooth muscles that control the state of relaxation or contraction of coronary arteries work. We know that calcium is one agent that is involved—it can enter the cell through voltage-regulated channels. Also, hormones or agonists can trigger a receptor, which is coupled to G proteins, and release calcium from the sarcoplasmic reticulum from internal stores. So there are two ways to release calcium into the cell: from outside, or from release of the sarcoplasmic reticulum within the cell. The faster the muscle must contract, the more likely it is that the calcium is released from inside the cells (like in the case of the lobster antennae that moves very fast). In our heart muscle, it is smooth muscle and has slow contractions so much of the calcium comes from the outside via voltage gated channels.

We have four ways to produce relaxation.

1. We could block the channels through which calcium enters the cell, these are the calcium channel blockers. If you don’t get the calcium into the cells than you wont get so much contraction.

2. Another way would be to block beta-agonists, like epinephrine. Beta-blockers interfere with activation of adenyl cyclase, whereby the cascade occurs to activate contraction.

3. Another way is with nitrovasodilators, this is the most common way to produce relaxation. In this case, a vasodilator like nitroglycerine will interfere with the guanylyl cyclase system and cyclic GMP will be produced, activating the cyclic GMP protein kinase and produce relaxation.

4. Finally, you could activate potassium channels so that the resting potential is stabilized and voltage production is prevented, preventing the opening of the calcium channels, and producing relaxation.

Category: Pharmacology Notes