Decreased Density of Mesenteric Arteries but not of Myocardial Endothelin Receptors and Function in Rats with Chronic Ischemic Heart Failure

Fu, Lei; Sun, Xingshu; Hedner, Thomas; Feng, Qingping; Liang, Qi-Ming; Hoebeke, Johan; Hjalmarson, Å

doi:10.1097/00005344-199308000-00001

Cited by 22 publications

(12 citation statements)

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“…Local activation of the endothelin system has been well demonstrated in a number of animal and human studies. [23][24][25] Thus, short-term blockade of the receptor may similarly demonstrate an attenuated vascular response, as occurred in the present study. This possibility is supported by the recent observation 10 of a decreased vasodilator response to ETRA in patients with congestive heart failure, a condition in which the endothelin system is clearly activated, both locally and systemically.…”

Section: Discussionsupporting

confidence: 77%

“…17 Blunted vasoconstrictor effects of exogenous endothelin-1 have been observed in many (but not all) studies of patients with essential hypertension, 18,19 chronic heart failure, 20 diabetes mellitus, 21 and chronic renal failure. 22 Such changes may be related to receptor downregulation 23 or postreceptor translational changes in the setting of local activation of the agonist. Local activation of the endothelin system has been well demonstrated in a number of animal and human studies.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Endothelin Blockade on Basal and Stimulated Forearm Blood Flow in Patients With Essential Hypertension

2002

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Abstract-Endothelin receptor antagonism lowers blood pressure in patients with essential hypertension, but the contribution of the endothelin system to increased vascular tone in these patients remains controversial. We used strain-gauge venous plethysmography to measure changes in basal and metabolically stimulated (peak reactive hyperemia [PRH]) forearm blood flow (FBF) induced by continuous intrabrachial infusion of SB 209670, a dual endothelin type A/endothelin type B receptor antagonist (ETRA) in 11 patients with hypertension and 12 healthy age-matched control subjects. In both groups, ETRA caused significant vasodilation (increase in FBF compared with baseline over the last 30 minutes of ETRA infusion: 75Ϯ12% in control subjects, 40Ϯ13% in hypertension patients; PϽ0.01 for both groups). By repeated-measures ANOVA, there was no greater increase in FBF after ETRA in hypertension patients compared with control subjects. In addition, FBF responses to PRH, expressed as percent change from baseline (prePRH), were similar in both groups (control subjects: preETRA, 1381Ϯ222%; during ETRA, 921Ϯ178%; and hypertension patients: preETRA, 1232Ϯ221%: during ETRA, 865Ϯ285%). We conclude that basal and stimulated vasodilation induced by short-term ETRA infusion in the forearm vasculature of hypertension patients is not increased compared with that of control subjects. An enhanced contribution of the endothelin system to vascular tone in hypertension patients could not be demonstrated using this experimental approach. There has, however, been some uncertainty regarding the contribution of ET-1 to the pathogenesis and/or progression of essential hypertension in man. The development of specific endothelin receptor antagonists (ETRAs) has enabled clinical investigators to further assess this contribution.Chronic (4-week) administration of an ETRA (bosentan) lowers blood pressure in patients with essential hypertension, 2 but whether the endothelin system is specifically involved in the increased vascular tone of these patients remains controversial. 3 Local intraarterial infusion of an ETRA into a vascular bed, with measurement of effects on resting blood flow, has been used in an attempt to address this specific question. In one such study, infusion of a selective ET A receptor antagonist into the forearm vasculature of patients with hypertension caused significant vasodilation; this was greater than that observed in normal subjects. 4 However, this difference was largely accounted for by the absence of significant vasodilation in the normal subjects, a finding at odds with a number of previous studies, which have consistently observed substantial vasodilation to an ET A antagonist in these subjects. [5][6][7][8][9][10] In addition, the contribution of ET-1 to the vasodilator response to metabolic stimuli such as postischemic reactive hyperemia has not been previously determined in patients with hypertension.In an attempt to clarify the above issues, the present study sought to compare the effect of a potent dual ET A /ET B ...

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Effect of Endothelin Blockade on Basal and Stimulated Forearm Blood Flow in Patients With Essential Hypertension

2002

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“…Moreover, differences in the regulation of ET receptors among tissues and models of hypertension have been reported (Haizer et al, 1994) and could account for the absence of modulation in SHRSP ventricle tissues. Fu et al (1993) observed a decreased density of ET receptors in mesenteric arteries but not in myocardium of rats with chronic ischaemic heart failure which is known to be accompanied by increased ET-1 immunoreactivity. Furthermore, it has been reported that some stimuli, such as All, induce ET-1 overexpression and up-regulation of ET receptors Kanno et al, 1993).…”

Section: Discussionmentioning

confidence: 80%

Action of the calcium channel blocker lacidipine on cardiac hypertrophy and endothelin‐1 gene expression in stroke‐prone hypertensive rats

Féron

Salomone

Godfraind

1996

British J Pharmacology

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1 The tissue-protective effects of calcium channel blockers in hypertension are not well dissociated from their effect on systolic blood pressure (SBP). We have previously shown that lacidipine, a dihydropyridine-type calcium antagonist, reduced the cardiac hypertrophy and the cardiac endothelin-1 (ET-1) gene overexpression occurring in salt-loaded stroke-prone spontaneously hypertensive rats (SL-SHRSP), an effect occurring without systolic blood pressure (SBP) change. In the present study, we have examined whether this action was dose-related and if it could be associated with ET receptor changes. The action of lacidipine was also examined in control SHRSP and in Wistar Kyoto rats (WKY). 2 The daily dose of 0.3 mg kg-' lacidipine which did not lower SBP but significantly prevented ventricle hypertrophy and cardiac preproET-1-mRNA expression in SL-SHRSP was inactive in control SHRSP. With the higher dose of lacidipine (1 mg kg-' day-'), we observed a further reduction of cardiac hypertrophy and of ET-1 gene expression in SL-SHRSP and a significant effect on those parameters in control SHRSP but only a small reduction of SBP in both groups. 3 In WKY, salt loading did not induce change in SBP or increase of cardiac ET-1 gene expression and ventricle mass. In these normotensive rats, lacidipine (1 mg kg-' day-') did not modulate the basal preproET-1-mRNA expression and did not affect SBP or heart weight. 4 The maximum binding capacity (Bmax) and the dissociation constant (KD) of ['25I]-ET-1 binding and the relative proportion of low-and high-affinity binding sites for ET-3 were not significantly affected by salt loading or lacidipine treatment in SHRSP. 5 These results show that lacidipine exerted a dose-related inhibition of ventricle hypertrophy and preproET-1-mRNA expression in SHRSP and indicate that this effect was unrelated to SBP changes. The dose-dependency of this inhibition suggests that salt-induced cardiac hypertrophy could be related to ET-1 gene overexpression. The results further show that ET receptor changes are not involved in the pathophysiological process studied here.

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“…Although improvements in peripheral vascular function have been observed following exercise regimens in human HF (18,22,43,53), the impact of exercise on the coronary vasculature has not been studied. Functional inadequacies of the peripheral and coronary vasculature, including altered reactions to mediators of vasoconstriction, such as ET-1, are well established in HF (8,21,32,33,46,49), implying exercise-dependent benefits extending to the coronary vasculature could directly impact LV function in HF. Much of the available literature demonstrates blunted coronary responsiveness to ET-1, as seen in a dog model of HF (8), and also following myocardial infarction in swine (35).…”

Section: Discussionmentioning

confidence: 99%

“…coronary circulation; vascular smooth muscle; potassium channels; heart failure CORONARY VASCULAR DYSFUNCTION is a hallmark feature of the progression to heart failure (HF). Altered responsiveness to mediators of vascular tone, such as endothelin-1 (ET-1), have been observed and may contribute to this phenomena (8,21,32,33,46,49). Impaired coronary vascular function can have profound effects on myocardial oxidative capacity and function and may play a significant role in the inability of the failing heart to respond to situations of increasing stress.…”

mentioning

confidence: 99%

Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca²⁺-sensitive K⁺ current in miniature swine with LV hypertrophy

Emter

Tharp²,

Ivey³

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Emter CA, Tharp DL, Ivey JR, Ganjam VK, Bowles DK. Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca 2ϩ -sensitive K ϩ current in miniature swine with LV hypertrophy. Am J Physiol Heart Circ Physiol 301: H1687-H1694, 2011. First published August 12, 2011 doi:10.1152/ajpheart.00610.2011.-Coronary vascular dysfunction has been observed in several models of heart failure (HF). Recent evidence indicates that exercise training is beneficial for patients with HF, but the precise intensity and underlying mechanisms are unknown. Left ventricular (LV) hypertrophy can play a significant role in the development of HF; therefore, the purpose of this study was to assess the effects of low-intensity interval exercise training on coronary vascular function in sedentary (HF) and exercise trained (HF-TR) aortic-banded miniature swine displaying LV hypertrophy. Six months postsurgery, in vivo coronary vascular responses to endothelin-1 (ET-1) and adenosine were measured in the left anterior descending coronary artery. Baseline and maximal coronary vascular conductance were similar between all groups. ET-1-induced reductions in coronary vascular conductance (P Ͻ 0.05) were greater in HF vs. sedentary control and HF-TR groups. Pretreatment with the ET type A (ETA) receptor blocker BQ-123 prevented ET-1 hypersensitivity in HF animals. Whole cell voltage clamp was used to characterize composite K ϩ currents (IKϩ) in coronary smooth muscle cells. Raising internal Ca 2ϩ from 200 to 500 nM increased Ca 2ϩ -sensitive K ϩ current in HF-TR and control, but not HF animals. In conclusion, an ETA-receptor-mediated hypersensitivity to ET-1, elevated resting LV wall tension, and decreased coronary smooth muscle cell Ca 2ϩ -sensitive IKϩ was found in sedentary animals with LV hypertrophy. Low-intensity interval exercise training preserved normal coronary vascular function and smooth muscle cell Ca 2ϩ -sensitive IKϩ, illustrating a potential mechanism underlying coronary vascular dysfunction in a large-animal model of LV hypertrophy. Our results demonstrate the potential clinical impact of exercise on coronary vascular function in HF patients displaying pathological LV hypertrophy. coronary circulation; vascular smooth muscle; potassium channels; heart failure CORONARY VASCULAR DYSFUNCTION is a hallmark feature of the progression to heart failure (HF). Altered responsiveness to mediators of vascular tone, such as endothelin-1 (ET-1), have been observed and may contribute to this phenomena (8,21,32,33,46,49). Impaired coronary vascular function can have profound effects on myocardial oxidative capacity and function and may play a significant role in the inability of the failing heart to respond to situations of increasing stress. The mechanism by which this occurs remains unclear. Considerable evidence exists indicating that profound modulation of both cardiomyocyte and smooth muscle cell electrophysiological phenotype are involved in cardiovascular disease (36, 47, 51). Calcium-activated K ϩ (K Ca...

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Decreased Density of Mesenteric Arteries but not of Myocardial Endothelin Receptors and Function in Rats with Chronic Ischemic Heart Failure

Cited by 22 publications

References 0 publications

Effect of Endothelin Blockade on Basal and Stimulated Forearm Blood Flow in Patients With Essential Hypertension

Effect of Endothelin Blockade on Basal and Stimulated Forearm Blood Flow in Patients With Essential Hypertension

Action of the calcium channel blocker lacidipine on cardiac hypertrophy and endothelin‐1 gene expression in stroke‐prone hypertensive rats

Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca²⁺-sensitive K⁺ current in miniature swine with LV hypertrophy

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Decreased Density of Mesenteric Arteries but not of Myocardial Endothelin Receptors and Function in Rats with Chronic Ischemic Heart Failure

Cited by 22 publications

References 0 publications

Effect of Endothelin Blockade on Basal and Stimulated Forearm Blood Flow in Patients With Essential Hypertension

Effect of Endothelin Blockade on Basal and Stimulated Forearm Blood Flow in Patients With Essential Hypertension

Action of the calcium channel blocker lacidipine on cardiac hypertrophy and endothelin‐1 gene expression in stroke‐prone hypertensive rats

Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca2+-sensitive K+ current in miniature swine with LV hypertrophy

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Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca²⁺-sensitive K⁺ current in miniature swine with LV hypertrophy