Synergetic antioxidant and vasodilatory action of carbon monoxide in angiotensin II - induced cardiac hypertrophy.

Abstract

The aim of this study was to determine the effects of carbon monoxide (CO) at a nontoxic low concentration on the cardiac and vascular hypertrophic response and reactive oxygen species generation, compared with the action of a vasodilator, hydralazine. Twelve- to 16-week-old low-density lipoprotein receptor knockout mice were subjected to angiotensin II (Ang II) infusion using osmotic minipumps (Ang II group; n=11) for 2 weeks. Controls were administered saline (n=10). Animals were exposed to CO in a chamber at 60 ppm for 2 hours per day with or without Ang II infusion (Ang II+CO group, n=10; CO group, n=9). Hydralazine was administered with Ang II infusion (n=10). Animals exhibited elevated arterial carboxyhemoglobin after CO exposure. Although the CO exposure did not affect systolic blood pressure without Ang II infusion, the hypertensive response after Ang II infusion was significantly attenuated by CO. Accordingly, the mice in the Ang II+CO group showed lesser left ventricular hypertrophy compared with those in the Ang II group. CO treatment also attenuated aortic hypertrophy. Interestingly, these changes were accompanied by the reduction of reactive oxygen species production, p47(phox) and p67(phox) subunit expressions of reduced nicotinamide-adenine dinucleotide phosphate oxidase, and Akt phosphorylation. Although hydralazine showed stronger antihypertensive action, superior inhibition on cardiac hypertrophy was obtained by CO (P<0.05). Furthermore, Ang II-dependent myocardial reactive oxygen species generation was more effectively suppressed by CO. Low-dose exogenous CO treatment attenuates Ang II-dependent reactive oxygen species generation, suggesting that appropriate CO administration alleviates hypertension and reduces organ hypertrophy mediated by Ang II.

• Authors: Atsushi Kobayashi, Kazunobu Ishikawa, Hayato Matsumoto, Satoshi Kimura, Yoshiyuki Kamiyama, Yukio Maruyama
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 50 Issue 6 Pg. 1040-8 (Dec 2007) ISSN: 1524-4563 [Electronic] United States
• PMID: 17923586 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Lipid Peroxides
• Reactive Oxygen Species
• Receptors, LDL
• Vasodilator Agents
• Angiotensin II
• Hydralazine
• Carbon Monoxide
• Carboxyhemoglobin
• NADPH Oxidases
• Proto-Oncogene Proteins c-akt

Topics

• Angiotensin II (pharmacology)
• Animals
• Antioxidants (pharmacology)
• Aorta (pathology)
• Blood Pressure (drug effects)
• Carbon Monoxide (pharmacology)
• Carboxyhemoglobin (analysis)
• Cardiomegaly (prevention & control)
• Hydralazine (pharmacology)
• Hypercholesterolemia (chemically induced)
• Lipid Peroxides (blood)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NADPH Oxidases (metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Reactive Oxygen Species (metabolism)
• Receptors, LDL (physiology)
• Vasodilator Agents (pharmacology)