© 2001 American Heart Association, Inc.
Vascular Biology |
Role of Sex Differences and Effects of Endothelial NO Synthase Deficiency in Responses of Carotid Arteries to Serotonin
From the Departments of Internal Medicine and Pharmacology, The Cardiovascular Center, The University of Iowa, and Veterans Administration Medical Center, Iowa City, Iowa.
Correspondence to Kathryn G. Lamping, PhD, Medical Services (111), VA Medical Center, 601 Highway 6 West, Iowa City, IA 52246. E-mail kathryn-lamping{at}uiowa.edu
Abstract—We
examined the hypothesis that contraction of the carotid arteries to
serotonin is normally inhibited by
endothelial NO synthase (eNOS) and is enhanced in mice
lacking the gene for eNOS. Because the influence of eNOS may vary with
the sex of the mouse, we also tested whether responses to
serotonin were dependent on sex. We studied carotid
arteries in vitro from littermate control
(eNOS+/+) mice, heterozygous
(eNOS+/-) mice, and homozygous
eNOS-deficient (eNOS-/-) mice (male and
female). Contraction to serotonin was greater in male
eNOS+/+ mice than in female
eNOS+/+ mice. In male mice, contraction to
serotonin increased by 
40% and 2.5-fold in male
eNOS+/- and
eNOS-/- mice, respectively. Contraction
to serotonin was more than doubled in female
eNOS+/- mice and increased >5-fold in
arteries from eNOS-/- mice. In contrast,
maximum vasoconstriction to U46619 was similar in male and female
eNOS+/+,
eNOS+/-, and
eNOS-/- mice. Relaxation to
acetylcholine was not different in male and female
eNOS+/+ or
eNOS+/- mice but was absent in
eNOS-/- mice. These findings suggest
that the contraction of carotid arteries to serotonin is
influenced by the sex of the animal. eNOS deficiency in gene-targeted
mice is associated with enhanced contraction to serotonin,
particularly in female mice, providing direct evidence that eNOS is a
major determinant of vascular effects of serotonin. The
results with eNOS+/- mice suggest a
"gene-dosing" effect for vascular responses to
serotonin.
Key Words: NO synthase • acetylcholine • thromboxane • mice • genetically altered mice
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