Question

14. Huntington’s disease (HD) is a fatal neurodegenerative disorder. As the disease progresses, HD patients exhibit abnormalities in both of their efferent motor divisions. Interestingly, HD patients seem to have impairments in their ability to regulate Mean Arterial Pressure. For example, you are treating a patient who always gets lightheaded and/or faints immediately upon standing. The issue is so pronounced that they literally sleep standing up!

    1. (a) (2 points) What change in MAP occurs for someone who stands up? Please use one word for this answer; do not explain why, as the rest of the question will help you determine why.

    2. (b) (13 points) How would the body normally compensate for this change in MAP? Be sure to outline the steps, pathways, and targets that would be involved, and indicate how those targets would respond to restore MAP. DO NOT INCLUDE ANY CELLULAR MECHANISMS HERE. This means that I want you to tell me HOW the targets activity changes (it increases/decreases contractility, e.g.); do NOT tell me how that change is accomplished (no need to tell me that this transmitter does this thing to keep that channel open.) This is important: if you are not sure how to answer this question, email DMW.

    3. (c) (7 points) Please detail the cellular mechanism for the response that occurs due to smooth muscle ONLY that will contribute to addressing the change in MAP you stated for part a above. For full credit, you must tell me the normal functioning of smooth muscle AND how that response is modified in response to steps outlined in part b.

Answer 1

1. Mean arterial pressure (MAP) is defined as average arterial pressure during one cardiac cycle; systole and diastole. When a person stands up the mean arterial pressure decreases.

2. MAP is regulated through a combined effect of different organ systems;

a. Cardiovascular system regulates Map through cardiac output and systemic vascular resistance. Intravascular volume, preload, afterload, myocardial contractility, heart rate and conduction velocity are factors that regulate cardia output. Similarly vasoconstriction and dilation regulate systemic vascular resistance.

Systemic vascular resistance is determined through the radius of blood vessels. Blood vessels lined by endothelial cells acts in response to different vasoactive substance that signals either to contract and dilate the blood vessels.

As MAP falls during standing, the vascular smooth muscle cells contract. Similarly baroreceptors stimulation is decreased during decreased MAP.

b. The renal system regulates MAP by increasing the plasma volume through sodium reabsorption in distal convoluted tubules of kidneys. This is the result of renin-angiotensin-aldosterone system that results in a cascade of reaction that ends with release of aldosterone

c. Baroreceptors acts as autonomic nervous system and are located in the carotid sinus and aortic arch. These help regulate MAP by affecting both cardiac output and systemic vascular resistance.

3. During an increase in MAP endothelial cells increases synthesis of Nitric oxide (NO). NO diffuses into vascular smooth muscle cells and activate guanylyl cyclase that dephosphorylates GTP to cGMP. cGMP acts as secondary messenger and leads to relaxation of smooth muscle and dilation of blood vessels.

When MAP decreases, endothelin, a vasoactive compound is produced by the endothelial cells. Endothelin diffuses into the vascular smooth muscle cells and binds to ET-1 receptor that is coupled with Gq-receptor. This association result in formation of inositol triphosphate (IP3) and release of calcium from sarcoplasmic reticulum. This signaling results in smooth muscle contraction and blood vessel constriction.