Question: Endothelin is a vasoactive peptide involved in a variety of processes, including the control of blood flow. Endothelin is capable of binding to two different receptors. There are receptors for endothelin located on smooth muscle (ETA) and receptors for endothelin located on vascular endothelium (ETB). When endothelin binds to ETA, it initiates vasoconstriction by narrowing blood vessels. However, when endothelin binds to ETB, vasodilation occurs due to the widening of blood vessels. The activity of the ETB receptor seems to counterregulate the ETA effects and prevents excessive vasoconstriction.
Drug $X$ is a selective receptor antagonist for endothelin. It is designed to bind preferentially to certain endothelin receptors. Drug $\mathrm{Y}$ is another selective receptor antagonist for endothelin. It is also designed to preferentially bind to one of the endothelin receptors. Researchers are hopeful that drugs $\mathrm{X}$ and $\mathrm{Y}$ will be of value in the treatment of conditions such as pulmonary arterial hypertension (PAH). In PAH, excess endothelin is produced, which causes an increase in blood pressure within the pulmonary arteries. Normal pressure in the pulmonary arteries is expected to be about $14 \mathrm{~mm} \mathrm{Hg}$, and pressure at or above $25 \mathrm{~mm}$ Hg constitutes PAH. Both drugs have been tested in patients with PAH. There were five patients in each group. At the end of the study, the percent decrease in mean pulmonary artery pressure was measured for each patient and reported in the table.
\begin{tabular}{cccc}
\hline Patient & Drug X & DrugY & Placebo \\
\hline 1 & $+10 \%$ & $-10 \%$ & $+5 \%$ \\
2 & $+3 \%$ & $-5 \%$ & $0 \%$ \\
3 & $-5 \%$ & $+2 \%$ & $+13 \%$ \\
4 & $+2 \%$ & $0 \%$ & $-4 \%$ \\
5 & $0 \%$ & $-7 \%$ & $-2 \%$ \\
Average decrease & $+2 \%$ & $-4 \%$ & $+2.4 \%$ \\
\hline
\end{tabular}
Suppose a patient suffers from chronic systolic and diastolic hypertension due to an inherited defect in an endothelin receptor. How would the kidneys attempt to alleviate the hypertension?

Options:
A. by decreasing water absorption in the nephrons
B. by decreasing urine output thus increasing blood volume
C. by increasing the amount of aldosterone secreted from the adrenal glands
D. by increasing the amount of antidiuretic hormone secreted from the pituitary gland
Answer: This question expects you to be able to consider how the kidneys are involved in regulating blood volume and blood pressure. Water that is reabsorbed in the nephrons returns to the bloodstream to increase plasma volume, which in turn increases blood pressure as the volume of blood increases. When the nephrons absorb more water to increase blood volume, the urine volume decreases. The two hormones aldosterone and antidiuretic hormone help increase the amount of water reabsorbed by nephrons, which in turn decreases urine volume. In order to reduce blood pressure, the kidneys can decrease the amount of water reabsorbed by the nephrons. The less water reabsorbed means there will be less blood volume and less blood pressure. This would ultimately increase urine volume. The question asks how the kidneys might try to reduce hypertension. This would mean that we want less water reabsorbed into the blood, which would decrease blood volume and blood pressure. To do this, urine volume would have to increase. The correct answer is A.