Nicorandil promotes myocardial capillary and arteriolar growth in the failing heart of Dahl salt-sensitive hypertensive rats

Jinglan Xu, Kohzo Nagata, Koji Obata, Sahoko Ichihara, Hideo Izawa, Akiko Noda, Tetsuro Nagasaka, Mitsunori Iwase, Tomoki Naoe, Toyoaki Murohara, Mitsuhiro Yokota

Research output: Contribution to journalArticle

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Abstract

Long-term administration of vasodilators increases shear stress, which is thought to be important for vascular growth in the heart. Nicorandil, an activator of ATP-sensitive potassium channels with a nitrate-like action, is a potent vasodilator. We have now investigated the effects of nicorandil on vascular growth and gene expression in the failing heart of Dahl salt-sensitive (DS) hypertensive rats. DS rats fed a high-salt diet from 6 weeks of age develop concentric cardiac hypertrophy secondary to hypertension at 11 weeks, followed by heart failure at 18 weeks. DS rats on such a diet were treated with a nonantihypertensive oral dose of nicorandil (6 mg/kg per day) or vehicle from 11 to 18 weeks of age. Treatment of DS rats with nicorandil improved cardiac function and attenuated the development of heart failure. Myocardial capillary and arteriolar densities did not differ between vehicle-treated DS rats and age-matched controls. The abundance of mRNAs for endothelial NO synthase (eNOS), vascular endothelial growth factor (VEGF), the VEGF receptor Flt-1, and basic fibroblast growth factor (bFGF) in the myocardium was markedly reduced in vehicle-treated DS rats compared with controls. Treatment of DS rats with nicorandil greatly increased capillary and arteriolar densities and inhibited the downregulation of eNOS, VEGF, fms-like tyrosin kinase-1, and bFGF gene expression. This, nicorandil stimulates coronary capillary and arteriolar growth and thereby likely suppresses the development of heart failure in DS rats. Nicorandil may prove beneficial for the treatment of hypertensive heart failure as well as of ischemic heart disease.

Original languageEnglish
Pages (from-to)719-724
Number of pages6
JournalHypertension
Volume46
Issue number4
DOIs
Publication statusPublished - 01-10-2005

Fingerprint

Nicorandil
Inbred Dahl Rats
Growth
Heart Failure
Fibroblast Growth Factor 2
Vasodilator Agents
Nitric Oxide Synthase
Vascular Endothelial Growth Factor A
Blood Vessels
Diet
Vascular Endothelial Growth Factor Receptor-1
Gene Expression
KATP Channels
Cardiomegaly
Nitrates
Myocardial Ischemia
Myocardium
Phosphotransferases
Down-Regulation
Salts

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Xu, Jinglan ; Nagata, Kohzo ; Obata, Koji ; Ichihara, Sahoko ; Izawa, Hideo ; Noda, Akiko ; Nagasaka, Tetsuro ; Iwase, Mitsunori ; Naoe, Tomoki ; Murohara, Toyoaki ; Yokota, Mitsuhiro. / Nicorandil promotes myocardial capillary and arteriolar growth in the failing heart of Dahl salt-sensitive hypertensive rats. In: Hypertension. 2005 ; Vol. 46, No. 4. pp. 719-724.
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abstract = "Long-term administration of vasodilators increases shear stress, which is thought to be important for vascular growth in the heart. Nicorandil, an activator of ATP-sensitive potassium channels with a nitrate-like action, is a potent vasodilator. We have now investigated the effects of nicorandil on vascular growth and gene expression in the failing heart of Dahl salt-sensitive (DS) hypertensive rats. DS rats fed a high-salt diet from 6 weeks of age develop concentric cardiac hypertrophy secondary to hypertension at 11 weeks, followed by heart failure at 18 weeks. DS rats on such a diet were treated with a nonantihypertensive oral dose of nicorandil (6 mg/kg per day) or vehicle from 11 to 18 weeks of age. Treatment of DS rats with nicorandil improved cardiac function and attenuated the development of heart failure. Myocardial capillary and arteriolar densities did not differ between vehicle-treated DS rats and age-matched controls. The abundance of mRNAs for endothelial NO synthase (eNOS), vascular endothelial growth factor (VEGF), the VEGF receptor Flt-1, and basic fibroblast growth factor (bFGF) in the myocardium was markedly reduced in vehicle-treated DS rats compared with controls. Treatment of DS rats with nicorandil greatly increased capillary and arteriolar densities and inhibited the downregulation of eNOS, VEGF, fms-like tyrosin kinase-1, and bFGF gene expression. This, nicorandil stimulates coronary capillary and arteriolar growth and thereby likely suppresses the development of heart failure in DS rats. Nicorandil may prove beneficial for the treatment of hypertensive heart failure as well as of ischemic heart disease.",
author = "Jinglan Xu and Kohzo Nagata and Koji Obata and Sahoko Ichihara and Hideo Izawa and Akiko Noda and Tetsuro Nagasaka and Mitsunori Iwase and Tomoki Naoe and Toyoaki Murohara and Mitsuhiro Yokota",
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Xu, J, Nagata, K, Obata, K, Ichihara, S, Izawa, H, Noda, A, Nagasaka, T, Iwase, M, Naoe, T, Murohara, T & Yokota, M 2005, 'Nicorandil promotes myocardial capillary and arteriolar growth in the failing heart of Dahl salt-sensitive hypertensive rats', Hypertension, vol. 46, no. 4, pp. 719-724. https://doi.org/10.1161/01.HYP.0000185189.46698.15

Nicorandil promotes myocardial capillary and arteriolar growth in the failing heart of Dahl salt-sensitive hypertensive rats. / Xu, Jinglan; Nagata, Kohzo; Obata, Koji; Ichihara, Sahoko; Izawa, Hideo; Noda, Akiko; Nagasaka, Tetsuro; Iwase, Mitsunori; Naoe, Tomoki; Murohara, Toyoaki; Yokota, Mitsuhiro.

In: Hypertension, Vol. 46, No. 4, 01.10.2005, p. 719-724.

Research output: Contribution to journalArticle

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T1 - Nicorandil promotes myocardial capillary and arteriolar growth in the failing heart of Dahl salt-sensitive hypertensive rats

AU - Xu, Jinglan

AU - Nagata, Kohzo

AU - Obata, Koji

AU - Ichihara, Sahoko

AU - Izawa, Hideo

AU - Noda, Akiko

AU - Nagasaka, Tetsuro

AU - Iwase, Mitsunori

AU - Naoe, Tomoki

AU - Murohara, Toyoaki

AU - Yokota, Mitsuhiro

PY - 2005/10/1

Y1 - 2005/10/1

N2 - Long-term administration of vasodilators increases shear stress, which is thought to be important for vascular growth in the heart. Nicorandil, an activator of ATP-sensitive potassium channels with a nitrate-like action, is a potent vasodilator. We have now investigated the effects of nicorandil on vascular growth and gene expression in the failing heart of Dahl salt-sensitive (DS) hypertensive rats. DS rats fed a high-salt diet from 6 weeks of age develop concentric cardiac hypertrophy secondary to hypertension at 11 weeks, followed by heart failure at 18 weeks. DS rats on such a diet were treated with a nonantihypertensive oral dose of nicorandil (6 mg/kg per day) or vehicle from 11 to 18 weeks of age. Treatment of DS rats with nicorandil improved cardiac function and attenuated the development of heart failure. Myocardial capillary and arteriolar densities did not differ between vehicle-treated DS rats and age-matched controls. The abundance of mRNAs for endothelial NO synthase (eNOS), vascular endothelial growth factor (VEGF), the VEGF receptor Flt-1, and basic fibroblast growth factor (bFGF) in the myocardium was markedly reduced in vehicle-treated DS rats compared with controls. Treatment of DS rats with nicorandil greatly increased capillary and arteriolar densities and inhibited the downregulation of eNOS, VEGF, fms-like tyrosin kinase-1, and bFGF gene expression. This, nicorandil stimulates coronary capillary and arteriolar growth and thereby likely suppresses the development of heart failure in DS rats. Nicorandil may prove beneficial for the treatment of hypertensive heart failure as well as of ischemic heart disease.

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