Continuing with our examination of drugs that regulate cardiovascular function,
vasoconstrictors are drugs that increase smooth muscular contractility in blood vessels,
thereby increasing systemic vascular resistance, and by extension, blood pressure. As we learned
in the tutorial on bronchodilators, we can appreciate how sensitive air flow is towards
the luminal diameter of the respiratory system tissues. Understandably, this also applies to
the cardiovascular system and blood vessels. Vasoconstrictors or ‘pressor’ drugs are critical
in emergency medicine due to the extent that hypotension, or low blood pressure,
is considered to be an emergency that must be aggressively treated. The quantitative
benchmark for hypotension is less than 90 millimeters mercury systolic pressure,
the pressure experienced by the arteries while the heart is beating, or 60 millimeters mercury
diastolic pressure, the pressure in the arteries in between heartbeats. The reason hypotension is
important to treat rapidly and aggressively is due to blood flow dropping towards crucial organ
systems such as the brain, kidneys, and heart. If the passage of blood in these systems is reduced
for long enough, organ failure and death are possible. Hypotension can arise for a few
different reasons. A few examples are as follows. Hypovolemia, a state of extreme blood volume loss
from hemorrhage or drastic dehydration. Reduced cardiac output from conditions like heart
failure or damage to the myocardium. And reduced sympathetic tone arising from sepsis or drugs that
interact with the autonomic nervous system. Hemodynamics is a complicated topic,
and although these drugs increase arterial pressure, if the organ’s systemic pressure
also increases, the blood flow towards the organ will remain the same. Fortunately,
vasoconstrictors tend to increase blood pressure in blood vessels outside these critical organs
more than within the organ systems themselves. As a result of this, circulation in these critical
organs is increased down a pressure gradient. Now that we understand a bit about the background
of these drugs, we can learn how different vasoconstrictors increase blood pressure.
There are two main classes of vasoconstrictors. Alpha-1 adrenoceptor agonists, and vasopressin
receptor agonists. We have discussed some adrenoceptors in previous tutorials, and
thus may recall that the alpha adrenoceptor-1 is most highly expressed in vascular smooth muscle.
Like the other adrenoceptors it is a G protein coupled receptor, which couples through the
Gq signalling cascade. This signalling cascade has been described at length in the tutorial on
decongestants. But to summarize, Gq signalling leads to increased intracellular calcium ions,
leading to increased smooth muscle contractility, in turn leading to decreased blood vessel luminal
area. In this context, alpha-1 agonist pressors, such as Phenylephrine, are often administered
intravenously in an emergency, due to more appropriate fast onset pharmacokinetics.
The other class of vasoconstrictors, vasopressin receptor agonists, we have also encountered in
the previous tutorial, on volume regulating drugs. A commonly used vasoconstrictor in
this class is vasopressin. These are analogs of the natural peptide hormone also known as
anti-diuretic hormone. As we learned, this peptide is physiologically produced in the hypothalamus,
released by the pituitary gland, and acts on the V2 vasopressin receptor on collecting duct cells
of the nephron to increase the insertion of water transporting proteins known as aquaporins. This
leads to an increase of water re-absorption from the renal system into the cardiovascular system.
More fluid reabsorption understandably leads to increased blood pressure through increased
blood volume. However, the V1 vasopressin receptor on blood vessels is also activated,
and contributes heavily towards vasoconstriction. V1 also signals through Gq, which can
compound with alpha-1 adrenoceptor agonists. Like all other drugs, use of vasoconstrictors
needs to be carefully considered and patients need to be monitored when used in the case of
an emergency. This is because coronary arteries are susceptible to constriction, which may reduce
blood flow to parts of the myocardium, and cause angina, a type of chest pain. Use of vasopressin
especially needs to be carefully monitored because it may constrict coronary arteries
and increase the myocardium’s overall need of oxygen due to increased arterial pressure. With
vasoconstrictors now understood, let’s move on to examine their precise opposite, vasodilators.