Up-Regulation of Akt and eNOS Induces Vascular Smooth Muscle Cell Differentiation in Hypertension In Vivo
| Autor: | Susumu Matsuda, Masunori Matsuzaki, Masakazu Tanaka, Seiji Umemoto, Kyoko Umeji, Makoto Kubo, Shinji Kawahara |
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| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Vascular smooth muscle Nitric Oxide Synthase Type III Cell Protein Serine-Threonine Kinases Biology Rats Inbred WKY Muscle Smooth Vascular Enos In vivo Proto-Oncogene Proteins Rats Inbred SHR Internal medicine medicine Animals Protein kinase B Pharmacology Angiotensin II receptor type 1 Cell Differentiation biology.organism_classification Angiotensin II Rats Up-Regulation Cell biology Endocrinology medicine.anatomical_structure Vascular smooth muscle cell differentiation Hypertension cardiovascular system Nitric Oxide Synthase Cardiology and Cardiovascular Medicine Proto-Oncogene Proteins c-akt |
| Zdroj: | Journal of Cardiovascular Pharmacology. 45:367-374 |
| ISSN: | 0160-2446 |
| Popis: | Recent studies have shown that angiotensin II type 1 (AT1) receptor-mediated Akt activation induces vascular smooth muscle cell (VSMC) dedifferentiation in vitro. However, the critical signal transductions affecting the VSMC phenotype remain unclear in vivo. We examined whether signal transduction through AT1 receptor-mediated reactive oxygen species (ROS) could regulate the VSMC phenotype in stroke-prone spontaneously hypertensive rats (SHRSPs). Male SHRSPs were randomized and treated for 6 weeks with a vehicle, an ACE inhibitor cilazapril, or an AT1 receptor antagonist E4177. The 2 drugs showed equipotent effects on the blood pressure, aortic morphology, and collagen deposition. Both drugs also significantly reduced aortic NAD(P)H oxidase activity and p38MAPK and ERK expression, whereas p-Akt, eNOS, and SM2 were significantly increased in SHRSP aortas. Furthermore, E4177 was more effective than cilazapril at inducing VSMC differentiation by reducing NAD(P)H oxidase activity, and up-regulating p-Akt, eNOS, and SM2. Thus, an ACE inhibitor and an AT1 receptor antagonist inhibited VSMC dedifferentiation through inhibition of NAD(P)H oxidase activity and up-regulation of eNOS and Akt in SHRSP aortas, suggesting that in contrast to the in vitro experiments, AT1 receptor-mediated NAD(P)H oxidase-generated ROS, eNOS, and Akt might be crucial determinants for the VSMC phenotype in hypertension in vivo. |
| Databáze: | OpenAIRE |
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