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Updated: Sep 26, 2026
Mouse Adrenal Chromaffin Cell Isolation
Published on: January 5, 2007
Lessons from the adrenomedullin knockout mouse
Katsuyuki Ando1, Toshiro Fujita
1Department of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1 Hongo, Tokyo 113-8655, Bunkyoku, Japan.
Abstract:
Because vasolidator peptide adrenomedullin (AM) exhibits complicated action, we developed AM knockout mice in order to elucidate the physiological and pathophysiological role of AM. The AM(-/-) mice were embryonic lethal, so we could not evaluate directly the role of AM in this mutant mice. Thus, we loaded angiotensin II (AngII) and salt in AM(+/-) mice, which were viable and fertile. As a result, AngII and salt loading caused coronary vascular damage and left ventricular hypertrophy in AM(+/-) mice more greatly than AM(+/+) mice. Moreover, cuff placement of femoral artery stimulated intimal thickening more severely. This treatment increased local AM levels in AM(+/+) mice but not in AM(+/-) mice. The accelerated organ damage in AM(+/-) mice was accompanied with enhanced production of oxidative stress. Thus, our data suggest that intrinsic AM play a vascular protective role.
Insights
Adrenomedullin (AM), a vasodilator peptide, plays a crucial role in vascular protection. Our study shows that reduced AM levels exacerbate organ damage and oxidative stress, highlighting its protective function.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Physiology
Background:
- Adrenomedullin (AM) is a peptide vasodilator with complex biological actions.
- Understanding the physiological and pathophysiological roles of AM is essential for cardiovascular health.
- Previous studies on AM knockout mice were limited due to embryonic lethality.
Purpose of the Study:
- To elucidate the physiological and pathophysiological role of adrenomedullin (AM).
- To investigate the vascular protective effects of intrinsic AM in vivo.
- To determine the impact of AM deficiency on cardiovascular and organ damage.
Main Methods:
- Development of AM knockout mice and utilization of heterozygous AM(+/-) mice.
- Induction of cardiovascular stress using angiotensin II (AngII) and salt loading.
- Assessment of vascular damage, left ventricular hypertrophy, and intimal thickening.
- Measurement of local AM levels and oxidative stress markers.
Main Results:
- AM(-/-) mice were embryonic lethal, preventing direct evaluation.
- AM(+/-) mice exhibited significantly greater coronary vascular damage and left ventricular hypertrophy under AngII and salt loading compared to wild-type (AM(+/+)) mice.
- Femoral artery cuff placement led to more severe intimal thickening in AM(+/-) mice.
- Accelerated organ damage in AM(+/-) mice was associated with increased oxidative stress and impaired local AM production.
Conclusions:
- Intrinsic adrenomedullin (AM) plays a significant vascular protective role.
- AM deficiency exacerbates cardiovascular damage and oxidative stress.
- Targeting AM may offer therapeutic potential for vascular diseases.
