Dipyridamole-induced capillary growth in normal and hypertrophic hearts

Torry, Ronald J.; O’Brien, Donalee; Connell, P. M.; Tomanek, Robert J.

doi:10.1152/ajpheart.1992.262.4.h980

Cited by 25 publications

(21 citation statements)

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“…23 An increase in blood flow may enhance vascular growth through increases in shear stress, wall tension, or stretch. 13,24 Nicorandil induces vasodilation by opening K ATP channels and through its nitrate-like action. 1,2 We therefore hypothesized that chronic treatment with nicorandil might increase blood flow and stimulate coronary angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Nicorandil Promotes Myocardial Capillary and Arteriolar Growth in the Failing Heart of Dahl Salt-Sensitive Hypertensive Rats

Nagata

Okihara

et al. 2005

Hypertension

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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.

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Section: Discussionmentioning

confidence: 99%

“…[13][14][15][16] We hypothesized that long-term administration of nicorandil, a potent vasodilator, 1 might induce myocardial angiogenesis through stimulation of the production of angiogenic growth factors such as bFGF and VEGF, and that such an effect might contribute to the beneficial action of this drug in heart failure.…”

mentioning

confidence: 99%

Nicorandil Promotes Myocardial Capillary and Arteriolar Growth in the Failing Heart of Dahl Salt-Sensitive Hypertensive Rats

Nagata

Okihara

et al. 2005

Hypertension

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“…36,39 Further potential mechanisms of dipyridamole in stroke pathophysiology include anti-inflammatory actions and proangiogenic effects. 40,41 Clopidogrel. In a large clinical trial, clopidogrel reduced the composite endpoint of stroke, myocardial infarction, or vascular death compared with aspirin in high-risk patients.…”

Section: Citicolinementioning

confidence: 99%

Multifunctional Actions of Approved and Candidate Stroke Drugs

Minnerup

Schäbitz

2009

Neurotherapeutics

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Summary: Ischemic stroke causes brain damage by multiple pathways. Previous stroke trials have demonstrated that drugs targeting one or only a few of these pathways fail to improve clinical outcome after stroke. Drugs with multimodal actions have been suggested to overcome this challenge. In this review, we describe the mechanisms of action of agents approved for secondary prevention of ischemic stroke, such as antiplatelet, antihypertensive, and lipid-lowering drugs. These drugs exhibit considerable properties beyond their classical mechanisms, including neuroprotective and neuroregenerative properties. In addition, candidate stroke drugs currently studied in clinical phase III trials are described. Among these, albumin, hematopoietic growth factors, and citicoline have been identified as promising agents with multiple mechanisms. These drugs offer hope that additional treatment options for the acute phase after a stroke will become available in the near future.

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“…However, adult animals display attenuated myocardial capillary growth compared with young postnatal animals with pressure-overload hypertrophy (43,45,46). In the young, concurrent growth of the myocardium and coronary microvasculature is present, such that normal capillary density and coronary blood flow reserve are preserved (43).…”

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confidence: 99%

Effects of gestational age on myocardial blood flow and coronary flow reserve in pressure-loaded ovine fetal hearts

Dalshaug¹,

Scholz

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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. Effects of gestational age on myocardial blood flow and coronary flow reserve in pressure-loaded ovine fetal hearts. Am J Physiol Heart Circ Physiol 282: H1359-H1369, 2002. First published December 6, 2001 10.1152/ajpheart.00686.2001.-To test the hypothesis that coronary flow and coronary flow reserve are developmentally regulated, we used fluorescent microspheres to investigate the effects of acute (6 h) pulmonary artery banding (PAB) on baseline and adenosine-enhanced right (RV) and left ventricular (LV) blood flow in two groups of twin ovine fetuses (100 and 128 days of gestation, term 145 days, n ϭ 6 fetuses/ group). Within each group, one fetus underwent PAB to constrict the main pulmonary artery diameter by 50%, and the other twin served as a nonbanded control. Physiological measurements were made 6 h after the surgery was completed; tissues were then harvested for analysis of selected genes that may be involved in the early phase of coronary vascular remodeling. Within each age group, arterial blood gas values, heart rate, and mean arterial blood pressure were similar between control and PAB fetuses. Baseline endocardial blood flow in both ventricles was greater in 100 than 128-day fetuses (RV: 341 Ϯ 20 vs. 230 Ϯ 17 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 ; LV: 258 Ϯ 18 vs. 172 Ϯ 23 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 , both P Ͻ 0.05). In both age groups, RV and LV endocardial blood flows increased significantly in control animals during adenosine infusion and were greater in PAB compared with control fetuses. After PAB, adenosine further increased RV blood flow in 128-day fetuses (from 416 Ϯ 30 to 598 Ϯ 33 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 , P Ͻ 0.05) but did not enhance blood flow in 100-day animals (490 Ϯ 59 to 545 Ϯ 42 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 , P Ͼ 0.2). RV vascular endothelial growth factor and Flk-1 mRNA levels were increased relative to controls (P Ͻ 0.05) in 128 but not 100-day PAB fetuses. We conclude that in the ovine fetus, developmentally related differences exist in 1) baseline myocardial blood flows, 2) the adaptive response of myocardial blood flow to acute systolic pressure load, and 3) the responses of selected genes involved in vasculogenesis to increased load in the fetal myocardium.hypertrophy; vascular endothelial growth factor; angiogenesis IN THE ADULT, adaptive growth of the heart in response to hypertrophic stimuli involves functional and morphological changes that are predictable depending on the stimuli (32, 33). Concomitant with the development of cardiac hypertrophy in the adult are qualitative and quantitative changes in gene expression, including upregulation of the so-called fetal cardiac genes, including ␤-myosin heavy chain, ␣-actin, and atrial natriuretic factor, and a reversion to fetal metabolic pathways for energy production (1,32,33,43). In the fetal heart, however, the molecular triggers for increasing ventricular mass in response to increased load are poorly understood and may be quite different from those in the adult, particularly given the ability of the fetal heart to increase mass by both hypertrop...

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Dipyridamole-induced capillary growth in normal and hypertrophic hearts

Cited by 25 publications

References 0 publications

Nicorandil Promotes Myocardial Capillary and Arteriolar Growth in the Failing Heart of Dahl Salt-Sensitive Hypertensive Rats

Nicorandil Promotes Myocardial Capillary and Arteriolar Growth in the Failing Heart of Dahl Salt-Sensitive Hypertensive Rats

Multifunctional Actions of Approved and Candidate Stroke Drugs

Effects of gestational age on myocardial blood flow and coronary flow reserve in pressure-loaded ovine fetal hearts

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