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Department of Physiology and Biophysics and Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi 39216
Gender
differences in vascular reactivity have been suggested; however, the
cellular mechanisms involved are unclear. We tested the hypothesis that
the gender differences in vascular reactivity reflect gender-related,
possibly estrogen-mediated, distinctions in the expression and activity
of specific protein kinase C (PKC) isoforms in vascular smooth muscle.
Aortic strips were isolated from intact and gonadectomized male and
female Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats
(SHR). Isometric contraction was measured in endothelium-denuded aortic
strips. PKC activity was measured in the cytosolic and
particulate fractions, and the amount of PKC was measured using Western
blots and isoform-specific anti-PKC antibodies. In intact male WKY
rats, phenylephrine (Phe, 10
5 M) and phorbol
12,13-dibutyrate (PDBu, 106 M) stimulated contraction to
0.37 ± 0.02 and 0.42 ± 0.02 g/mg tissue wt, respectively.
The basal particulate/cytosolic PKC activity ratio was 0.86 ± 0.06, and Western blots revealed 
-, 
-, and 
-PKC isoforms. Phe
and PDBu increased PKC activity and caused significant translocation of
- and -PKC from the cytosolic to particulate fraction. In intact
female WKY rats, basal PKC activity, the amount of -, -, and
-PKC, the Phe- and PDBu-induced contraction, and PKC activity and
translocation of - and -PKC were significantly reduced compared
with intact male WKY rats. The basal PKC activity, the amount of -,
-, and -PKC, the Phe and PDBu contraction, and PKC activity and
- and -PKC translocation were greater in SHR than WKY rats. The
reduction in Phe and PDBu contraction and PKC activity in intact
females compared with intact males was greater in SHR (~30%) than
WKY rats (~20%). Phe and PDBu contraction and PKC activity were not
significantly different between castrated males and intact males but
were greater in ovariectomized (OVX) females than intact females.
Treatment of OVX females or castrated males with 17
-estradiol, but
not 17-estradiol, subcutaneous implants caused significant reduction
in Phe and PDBu contraction and PKC activity that was greater in SHR
than WKY rats. Phe and PDBu contraction and PKC activity in OVX females
or castrated males treated with 17-estradiol plus the estrogen
receptor antagonist ICI-182,780 were not significantly different from
untreated OVX females or castrated males. Thus a gender-related
reduction in vascular smooth muscle contraction in female WKY rats with
intact gonads compared with males is associated with reduction in the expression and activity of vascular -, -, and -PKC. The gender differences in vascular smooth muscle contraction and PKC activity are
augmented in the SHR and are possibly mediated by estrogen.
contraction; protein kinase C; sex hormones
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