Effects of cilnidipine on nitric oxide and endothelin-1 expression and extracellular signal-regulated kinase in hypertensive rats

Autor: Naohiko Kobayashi, Yousuke Mori, Shigefumi Nakano, Hiroaki Matsuoka, Tsutomu Kobayashi, Yusuke Tsubokou, Shin-ichiro Mita
Rok vydání: 2001
Předmět:
Male
Dihydropyridines
medicine.medical_specialty
Nitric Oxide Synthase Type III
Heart Ventricles
Receptor expression
Blotting
Western
urologic and male genital diseases
Nitric oxide
chemistry.chemical_compound
Enos
Internal medicine
polycyclic compounds
medicine
Extracellular
Animals
RNA
Messenger
cardiovascular diseases
Protein Precursors
Rats
Wistar
Protein kinase A
Mitogen-Activated Protein Kinase 1
Pharmacology
Mitogen-Activated Protein Kinase 3
Endothelin-1
biology
Receptors
Endothelin
Reverse Transcriptase Polymerase Chain Reaction
Chemistry
Endothelins
Body Weight
Hemodynamics
Organ Size
Cilnidipine
Calcium Channel Blockers
Receptor
Endothelin A
biology.organism_classification
Coronary Vessels
Endothelin 1
Rats
Endocrinology
Gene Expression Regulation
Hypertension
Mitogen-Activated Protein Kinases
Nitric Oxide Synthase
Endothelin receptor
hormones
hormone substitutes
and hormone antagonists
medicine.drug
Zdroj: European Journal of Pharmacology. 422:149-157
ISSN: 0014-2999
DOI: 10.1016/s0014-2999(01)01067-6
Popis: We evaluated the effects of cilnidipine, a long-acting Ca2+ channel antagonist, on endothelial nitric oxide synthase (eNOS), preproendothelin-1 and endothelin ET A receptor expression in the left ventricle, and evaluated the relations between these effects and coronary microvascular remodeling and extracellular signal-regulated kinases belonging to one subfamily of mitogen-activated protein kinases in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Cilnidipine (DOCA-cilnidipine, 1 mg/kg/day, subdepressor dose) or vehicle (DOCA-vehicle) was given after induction of DOCA-salt hypertension for 5 weeks. The eNOS mRNA and protein expression in the left ventricle was significantly lower in DOCA-vehicle than in control rats and significantly higher in DOCA-cilnidipine than in DOCA-vehicle rats. Preproendothelin-1 and endothelin ET A receptor expression levels and phospho-p42/p44 extracellular signal-regulated kinase activities were significantly increased in DOCA-vehicle compared with control rats and significantly suppressed in DOCA-cilnidipine compared with DOCA-vehicle rats. DOCA-vehicle rats showed a significant increase in the wall-to-lumen ratio, perivascular fibrosis and myocardial fibrosis, with all these parameters being significantly improved by cilnidipine. These results led us to conclude that phospho-p42/p44 extracellular signal-regulated kinase activities may contribute to the coronary microvascular remodeling of DOCA rats and that protective effects of cilnidipine on cardiovascular remodeling may be at least in part mediated by an increased eNOS expression and a decreased endothelin-1 and endothelin ET A receptor expression in the left ventricle.
Databáze: OpenAIRE
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