Sexual dimorphism in the blood pressure response to angiotensin II in mice after angiotensin-converting enzyme blockade.
BACKGROUND
The incidence of hypertension and progression of renal disease are greater in men than in women. Data suggest that there is a dimorphic response to angiotensin II (Ang II) in rats, with male rats exhibiting a greater increase in mean arterial pressure (MAP) than females. However, during endogenous renin-angiotensin system (RAS) blockade with angiotensin-converting enzyme (ACE) inhibition, female rats have a greater MAP response to Ang II. We tested whether female mice exhibit a greater MAP response to chronic Ang II during ACE inhibition.


METHODS
Twenty-week-old male and female C57BL/6J mice (n > or = 6/group), treated with enalapril (40 mg/kg/day in drinking water), were assigned to groups receiving either Ang II (800 ng/kg/min) or saline for 2 weeks. Enalapril treatment began 4 days before and continued throughout the experiment.


RESULTS
MAP was higher in male mice than female mice treated with enalapril and Ang II (male: 144 +/- 3 vs. female: 121 +/- 6 mm Hg, P < 0.05) and was not different between mice treated with enalapril alone (male: 99 +/- 3 vs. female: 100 +/- 3 mm Hg). F2-isoprostanes were not increased by Ang II; however, female mice had significantly higher levels than males. Renal cortical expression of catalase and Cu/Zn-superoxide dismutase (SOD) was not different between experimental groups. Urinary protein was higher in male mice when compared to females, but was not changed after treatment with Ang II in either group.


CONCLUSIONS
These data suggest that there are species and sex-specific differences in the mechanism of the blood pressure response to Ang II, even during ACE inhibition.
Venegas-Pont
Marcia
M
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Sartori-Valinotti
Julio C
JC
Glover
Porter H
PH
Reckelhoff
Jane F
JF
Ryan
Michael J
MJ
D000804:Angiotensin II / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002374:Catalase / Q000378:metabolism; D004357:Drug Synergism; D004656:Enalapril / Q000494:pharmacology*; D028441:F2-Isoprostanes / Q000652:urine; D005260:Female; D007672:Kidney Cortex / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011507:Proteinuria / Q000378:metabolism; D012727:Sex Characteristics; D013482:Superoxide Dismutase / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*
D000806:Angiotensin-Converting Enzyme Inhibitors; D028441:F2-Isoprostanes; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D004656:Enalapril; D002374:Catalase; D013482:Superoxide Dismutase