Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: Wild-type mice and animals deficient in guanylyl cyclase-A (GCA) and/or angiotensin receptors (AT(1) and AT(2) subtypes) were treated with hydralazine ( approximately 24 mg.kg(-1).day(-1) in drinking water) for 5 weeks. Cardiac mass and/or cardiomyocyte cross-sectional area, fibrosis (van Giessen-staining) and cardiac gene expression (real-time RT-PCR) were measured. KEY RESULTS:
Hydralazine lowered blood pressure in mice of all genotypes. However, this treatment increased the heart and left ventricular to body weight ratios, as well as cardiomyocyte cross-sectional area, and cardiac expression of atrial natriuretic peptide mRNA in mice lacking GCA. Hydralazine did not affect cardiac hypertrophy in wild-type mice and mice lacking either AT(1) or AT(2) receptors alone. However, the pro-hypertrophic effect of hydralazine was prevented in mice lacking both GCA and AT(2), but not GCA and AT(1) receptors. However, hydralazine did decrease cardiac collagen deposition and collagen I mRNA (signs of cardiac fibrosis) in mice that were deficient in GCA, or both GCA and AT(2) receptors. CONCLUSIONS AND IMPLICATIONS:
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Authors | Y Li, Y Saito, K Kuwahara, X Rong, I Kishimoto, M Harada, M Horiuchi, M Murray, K Nakao |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 159
Issue 5
Pg. 1133-42
(Mar 2010)
ISSN: 1476-5381 [Electronic] England |
PMID | 20136844
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Receptor, Angiotensin, Type 1
- Receptor, Angiotensin, Type 2
- Vasodilator Agents
- Hydralazine
- Receptors, Atrial Natriuretic Factor
- atrial natriuretic factor receptor A
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Topics |
- Animals
- Blood Pressure
(drug effects)
- Cardiomegaly
(etiology)
- Fibrosis
- Gene Expression
- Hydralazine
(adverse effects, pharmacology)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Myocytes, Cardiac
(drug effects, metabolism)
- Receptor, Angiotensin, Type 1
(genetics)
- Receptor, Angiotensin, Type 2
(genetics)
- Receptors, Atrial Natriuretic Factor
(genetics)
- Reverse Transcriptase Polymerase Chain Reaction
- Vasodilator Agents
(adverse effects, pharmacology)
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