University of California-Irvine

Contact: Andrew Porterfield, (949) 824-3969,

Alternate Explanation Points to Oft-Studied Molecule Nitric Oxide for Role
in Regulating Blood Pressure

Irvine, Calif. — Fainting after extended bed rest or by astronauts after
space flight may be caused by changes in the levels of a molecule known
for its role in regulating blood pressure, a UC Irvine College of Medicine
research team has found.

The study is the first to identify the molecule nitric oxide as a factor in
controlling blood pressure in different parts of the body when adapting
to the Earth’s gravity; most current research instead focuses on other
chemicals that control pressure. If the findings work in humans, they
could result in improved treatments for fainting spells that are often
experienced by patients after long periods of bed rest and by astronauts
returning from space. The findings appear in the July issue of the Journal
of Applied Physiology.

Prolonged bed rest or extended exposure to low gravity during space flight
often results in fainting spells, caused by changes in the way blood
pressure is regulated in the body. When standing on Earth, blood pressure
is usually higher in the feet than in the head; various chemicals work to
constrict blood vessels in the feet, forcing more blood to flow to the
brain. In a standing position under the effects of gravity, normal blood
pressure is usually much higher in the feet than in the head. But when a
person who has adapted to low gravity returns to Earth, blood vessels in
the lower body remain dilated, resulting in low pressure. Blood flow to
the brain then decreases, causing fainting.

A person standing up or an astronaut returning to Earth then experiences
fainting as blood pressure tries again to adapt to gravity. Most people
recovering from bed rest can take several weeks to re-adjust to a
standing position; astronauts wear constrictive “pressure suits” upon
returning to earth to prevent fainting.

Dr. Nosratola (Nick) Vaziri, professor of medicine, found that rats that
had adapted to an environment that simulated low gravity produced
significantly more of the enzyme that makes nitric oxide than did rats
in a normal gravity environment. Since nitric oxide dilates blood vessels,
the research suggests that the additional amounts of nitric oxide dilated
vessels in the lower body, lowering pressure in the head, which made
acclimation to a standing position more difficult and led to fainting.

“Previous research has focused on chemicals like norepinephrine, which
constrict blood vessels, because the researchers thought that gravity
must be preventing the chemicals from narrowing blood vessels and
forcing blood to flow to the head,” Vaziri said. “Instead of looking at
why constriction wasn’t effective, we looked at whether dilation was
too strong; what makes blood vessels in the feet and legs stay too wide,
causing the dramatic drops in blood pressure in the head and subsequent
fainting. This study led us to determine that nitric oxide was the
mechanism in the body that led to fainting after re-exposure to gravity.”

Vaziri’s team found that rats in a simulated low-gravity environment
produced more of the nitric oxide synthase enzyme, which produces nitric
oxide in the heart, blood vessels, kidneys and brain. Rats that were in
an environment sensitive to gravity had no increase in this enzyme. In
addition, when the rats in a low-gravity environment were injected
with a chemical called aminoguanidine, blood pressure increased.
Aminoguanidine inhibits the production of nitric oxide and has been
used to treat complications of diabetes without much success. Its
activity in this study indicated that the nitric oxide enzyme was the
contributing factor to the blood pressure changes and suggests that
chemicals that work similarly to it could be used to treat fainting spells
in people recovering from extended bed rest or returning astronauts.

Nitric oxide has been used in pharmaceutical products for decades; it
is the active ingredient in nitroglycerin, a drug long used to improve
circulation in the heart. Recently, researchers have uncovered its role
in controlling blood pressure, aiding the immune system to fight off
invading cells and processing memory in the brain. The sexual dysfunction
drug, Viagra, also regulates nitric oxide synthase.

“The levels of nitric oxide synthase increased dramatically in the
low-gravity rats; these molecules are helping us understand how blood
pressure changes in the head and lower body during space flight and after
extended bed rest,” said Vaziri. “We and other scientists would need to
see whether inhibitory chemicals have any other effects on the body
before we can determine if this phenomenon is also happening in humans.”

Vaziri’s colleagues in the study include UCI researchers Y. Ding, D.S.

Sangha and Ralph Purdy, professor of pharmacology at UCI. The study was
supported by a grant from NASA.