Enhanced angiotensin II type 2 receptor mechanisms mediate decreases in arterial pressure attributable to chronic low-dose angiotensin II in female rats

Sampson, A. K., Moritz, K. M., Jones, E. S., Flower, R. L., Widdop, R. E. and Denton, K. M. (2008) Enhanced angiotensin II type 2 receptor mechanisms mediate decreases in arterial pressure attributable to chronic low-dose angiotensin II in female rats. Hypertension, 52 4: 666-671. doi:10.1161/HYPERTENSIONAHA.108.114058


Author Sampson, A. K.
Moritz, K. M.
Jones, E. S.
Flower, R. L.
Widdop, R. E.
Denton, K. M.
Title Enhanced angiotensin II type 2 receptor mechanisms mediate decreases in arterial pressure attributable to chronic low-dose angiotensin II in female rats
Journal name Hypertension   Check publisher's open access policy
ISSN 0194-911X
Publication date 2008-01-01
Year available 2008
Sub-type Article (original research)
DOI 10.1161/HYPERTENSIONAHA.108.114058
Open Access Status
Volume 52
Issue 4
Start page 666
End page 671
Total pages 6
Editor Hall, J.E
Place of publication United States
Publisher Lippincott Williams and Wilkins
Language eng
Abstract The renin-angiotensin system is a far more complex enzymatic cascade than realized previously. Mounting evidence suggests sex-specific differences in the regulation of the renin-angiotensin system and arterial pressure. We examined the hemodynamic responses, angiotensin II receptor subtypes, and angiotensin-converting enzyme 2 gene expression levels after graded doses of angiotensin II in males and females. Mean arterial pressure was measured via telemetry in male and female rats in response to a 2-week infusion of vehicle, low-dose (50 ng/kg per minute SC) or high-dose (400 ng/kg per minute SC) angiotensin II. The effect of concurrent infusion of the angiotensin II type 2 receptor (AT(2)R) blocker (PD123319) was also examined. The arterial pressure response to high-dose angiotensin II was attenuated in females compared with males (24 +/- 8 mm Hg versus 42 +/- 5 mm Hg; P for the interaction between sex and treatment <0.002). Remarkably, low-dose angiotensin II decreased arterial pressure (11 +/- 4 mm Hg; P for the interaction between sex and treatment <0.02) at a dose that did not have an effect in males. This decrease in arterial pressure in females was abolished by AT2R blockade. Renal AT2R, angiotensin-converting enzyme 2, and left ventricular AT2R mRNA gene expressions were markedly greater in females than in males with a renal angiotensin II type 1a receptor: AT2R ratio of approximate to 1 in females. Angiotensin II infusion did not affect renal AT2R mRNA expression but resulted in significantly less left ventricular mRNA expression. Renal angiotensin-converting enzyme 2 mRNA expression levels were greater in females than in males treated with high-dose angiotensin II (approximate to 2.5 fold; P for the interaction between sex and treatment <0.05). In females, enhancement of the vasodilatory arm of the renin-angiotensin system, in particular, AT2R and angiotensin-converting enzyme 2 mRNA expression, may contribute to the sex-specific differences in response to renin-angiotensin system activation.
Keyword basic science
gender differences
gene expression/regulation
hypertension
angiotensin receptors
SPONTANEOUSLY HYPERTENSIVE-RATS
AT(2) RECEPTOR
SEX-DIFFERENCES
CONSCIOUS MICE
AT(1)
EXPRESSION
BLOCKADE
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 3340431
G06M2640
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Biomedical Sciences Publications
 
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Created: Wed, 18 Mar 2009, 22:04:35 EST