Endothelium-Dependent Relaxation Is Not Uniformly Impaired in Chronic Heart Failure

Baggia, Safia; Perkins, Keith D.; Greenberg, Barry

doi:10.1097/00005344-199703000-00013

Cited by 33 publications

(25 citation statements)

References 14 publications

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“…In agreement with other studies (Baggia et al, 1997;Bauersachs et al, 1999Bauersachs et al, , 2002Ceiler et al, 1999;Schä fer et al, 2003), we found no impairment of the endothelium-independent relaxation produced by SNP following infarction. However, we found impairment in the endothelium-dependent relaxation mediated by ACh in the tail vascular beds in Inf rats.…”

Section: Discussionsupporting

confidence: 93%

“…Impairments in endothelium-dependent relaxation have also been reported in patients with cardiovascular disease and chronic heart failure (Belardinelli, 2001;Annuk et al, 2003;Linke et al, 2003). Studies in different vessels using the rat infarction model for heart failure show either reductions or no changes in endothelial dependent relaxation, at different times after infarction (Teerlink et al, 1993;Baggia et al, 1997;Bauersachs et al, 1999Bauersachs et al, , 2002Ceiler et al, 1999;Indik et al, 2001;Annuk et al, 2003). Possibly, the endothelial dysfunction observed in heart failure may depend on its stage and the type of vessels studied (Fang and Marwick, 2002).…”

Section: Discussionmentioning

confidence: 99%

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Differences in Tail Vascular Bed Reactivity in Rats with and without Heart Failure following Myocardial Infarction

Pereira¹,

Sartório²,

Vassallo³

et al. 2004

J Pharmacol Exp Ther

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Myocardial infarction (MI) was induced in rats by coronary ligation to compare changes in vascular reactivity from animals that developed heart failure (InfHF) with those that did not (Inf). Infarct size was similar in both groups. In vitro preparations of tail vascular bed were used to investigate the vascular responses to acetylcholine, sodium nitroprusside, and phenylephrine. Acetylcholine-induced relaxation was impaired in the Inf group (53 Ϯ 2%, n ϭ 6) when compared with Sham (80 Ϯ 2%, n ϭ 6, P Ͻ 0.05). The maximal response (E max ) to phenylephrine increased in the Inf group (423 Ϯ 10 mm Hg, n ϭ 9, P Ͻ 0.01) and decreased in InfHF (279 Ϯ 10 mm Hg, n ϭ 7, P Ͻ 0.05) when compared with Sham (319 Ϯ 11 mm Hg, n ϭ 8). Regardless of endothelial integrity, E max to phenylephrine increased in the Inf, nitro-L-arginine methyl ester, and indomethacin groups. An increased release of a prostanoid vasodilator was detected in the Inf group. Differently, the InfHF group presented a reduction of the E max to phenylephrine and an increment of nitric oxide release. This study demonstrates that MI without heart failure impairs endothelium-dependent relaxation and increases the reactivity to phenylephrine. This increase seems to involve a muscular component. The endothelium participates with an increased release of a vasodilator prostanoid, possibly to compensate the increased smooth muscle response. When heart failure follows MI, the reactivity to phenylephrine decreases, possibly due to an increased nitric oxide release.Coronary artery ligation in rats has been used as a model of chronic left ventricular failure that closely mimics human condition (Hodsman et al., 1988). Indeed, compromised cardiac function (De Felice et al., 1989;Solomon et al., 1999) and increased peripheral resistance (Drexler and Lu, 1992;Schrier and Abraham, 1999) are found in this model. Systemic vasoconstriction can result from many compensatory mechanisms, including activation of the renin-angiotensin system, activation of the sympathetic nervous system, and alterations in the synthesis of local vascular factors (Zelis and Flaim, 1982;Gschwend et al., 2003).Much has been reported regarding endothelial dysfunction in postinfarction myocardial failure (Teerlink et al., 1993(Teerlink et al., , 1994Didion et al., 1997;Bauersachs et al., 1999;Indik et al., 2001;Gschwend et al., 2003), but there is no consensus regarding vascular function in heart failure due to heterogeneity of alterations in vascular reactivity. These alterations may depend on the duration of the disease and the type of artery studied (Stassen et al., 1997a). Despite much research on vascular reactivity in postinfarction heart failure, little is known concerning vascular reactivity in a chronic phase of myocardial infarction (MI), when heart failure is absent.The purpose of this study was, in the first place, to show that there are two animal models with similar infarction areas produced by coronary ligation: chronic MI without heart failure and with heart failure and, secondly, ...

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Differences in Tail Vascular Bed Reactivity in Rats with and without Heart Failure following Myocardial Infarction

Pereira¹,

Sartório²,

Vassallo³

et al. 2004

J Pharmacol Exp Ther

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“…Studies on the role of NO in the regulation of vasomotor tone in MI-induced LV dysfunction in rats indicate that between 4 and 16 wk after infarction, acetylcholine-or ADP-induced NOmediated relaxation of systemic conductance arteries (4,40,43,53,57) and resistance vessels (13) is reduced, although this is not an unequivocal finding (2,6). In contrast, basal NO production is maintained in systemic conductance arteries (2,43) and in resistance vessels in various regional vascular beds in vivo (6,10,13,21).…”

mentioning

confidence: 99%

Nitric oxide production is maintained in exercising swine with chronic left ventricular dysfunction

Haitsma

Merkus

Vermeulen

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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oxide production is maintained in exercising swine with chronic left ventricular dysfunction. Am J Physiol Heart Circ Physiol 282: H2198-H2209, 2002. First published February 21, 2002 10.1152/ajpheart.00834.2001 dysfunction caused by myocardial infarction (MI) is accompanied by endothelial dysfunction, most notably a loss of nitric oxide (NO) availability. We tested the hypothesis that endothelial dysfunction contributes to impaired tissue perfusion during increased metabolic demands as produced by exercise, and we determined the contribution of NO to regulation of regional systemic, pulmonary, and coronary vasomotor tone in exercising swine with LV dysfunction produced by a 2-to 3-wk-old MI. LV dysfunction resulted in blunted systemic and coronary vasodilator responses to ATP, whereas the responses to nitroprusside were maintained. Exercise resulted in blunted systemic and pulmonary vasodilator responses in MI that resembled the vasodilator responses in normal (N) swine following blockade of NO synthase with N -nitro-L-arginine (L-NNA, 20 mg/kg iv). However, L-NNA resulted in similar decreases in systemic (43 Ϯ 3% in N swine and 49 Ϯ 4% in MI swine), pulmonary (45 Ϯ 5% in N swine and 49 Ϯ 4% in MI swine), and coronary (28 Ϯ 4% in N and 35 Ϯ 3% in MI) vascular conductances in N and MI swine under resting conditions; similar effects were observed during treadmill exercise. Selective inhibition of inducible NO synthase with aminoguanidine (20 mg/kg iv) had no effect on vascular tone in MI. These findings indicate that while agonist-induced vasodilation is already blunted early after myocardial infarction, the contribution of endothelial NO synthase-derived NO to regulation of vascular tone under basal conditions and during exercise is maintained. coronary circulation; myocardial infarction; pulmonary circulation; regional blood flows; systemic circulation HEART FAILURE is accompanied by increased production of neurohormones such as norepinephrine, angiotensin II, and endothelin (19, 50), which serves to maintain arterial pressure by partially restoring cardiac output and increasing peripheral vascular resistance, to maintain perfusion of essential tissues like the brain and heart at the expense of renal, pancreatic, and intestinal blood flow. Several studies have indicated that also endothelial dysfunction, in particular a decreased production of nitric oxide (NO), contributes to an increased peripheral resistance in congestive heart failure (18,25,29,32,58). A loss of NO availability could aggravate left ventricular (LV) dysfunction due to the peripheral vasoconstriction-induced increase in LV afterload, coronary vasoconstriction, and increased myocardial O 2 consumption (15,34,47,58). In support of this concept, a decreased NO production coincides with the transition of LV dysfunction to overt congestive heart failure in models of pacing-induced heart failure (47, 58).Clinically, the most common cause for heart failure is myocardial infarction (MI). Studies on the role of NO in the regulation of vasomotor tone ...

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“…In comparison, a normal acetylcholine-induced relaxation with reduction of basal NO release was found in small mesenteric arteries from this rat HF model. 6,7 Conflicting data exist with regard to eNOS expression and activity in human beings with chronic HF. Increased cardiac expression of eNOS, however, with no increased eNOS activity, was found in end-stage human heart failure.…”

mentioning

confidence: 99%

Decreased Nitric Oxide Availability in Normotensive and Hypertensive Rats With Failing Hearts After Myocardial Infarction

et al. 2001

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Abstract-Endothelial NO synthase, being deficient in arginine and/or tetrahydrobiopterin, produces in addition to NO a significant concentration of superoxide (O 2 Ϫ ). We investigated whether such an imbalance between O 2 Ϫ and NO production is present in dysfunctional aortas of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) with failing hearts after myocardial infarction. Heart failure was induced by permanent occlusion of the left coronary artery, resulting in a large infarction of the free left ventricular wall. Eight weeks after myocardial infarction, when WKY and SHR had compensated heart failure and congestive heart failure, respectively, calcium ionophore-induced NO release (assessed by a NO-sensitive microsensor) from aortic endothelial cells was significantly reduced from 478Ϯ48 to 216Ϯ16 nmol/L and 693Ϯ131 to 257Ϯ53 nmol/L in WKY and SHR, respectively. Concomitantly, significant increases in calcium ionophore-stimulated O 2 Ϫ production (assessed by an electrochemical sensor) could be observed in aortic endothelial cells from infarcted WKY rats (22Ϯ3.2 versus sham, 10.1Ϯ1.2 nmol/L) and SHR (102Ϯ8 versus sham, 67Ϯ5 nmol/L). A dramatic increase in endothelial peroxynitrite concentration (chemiluminescence method) from 35Ϯ4 to 90Ϯ3 nmol/L for WKY and from 60Ϯ5 to 170Ϯ10 nmol/L for SHR also was detected. Thus, the markedly decreased NO availability probably caused by impaired endothelial NO synthase activity with enhanced O 2 Ϫ and peroxynitrite production appears to be attributable to endothelial dysfunction in normotensive rats with chronic heart failure and especially in hypertensive rats with severe congestive heart failure. Key Words: heart failure Ⅲ endothelium Ⅲ nitric oxide Ⅲ rats, spontaneously hypertensive Ⅲ rats, WKY N umerous studies showed that impaired endotheliumdependent vasodilation and cardiac dysfunction in heart failure (HF) appear to be attributable to decreased endothelial NO synthesis and/or possibly to increased NO degradation by enhanced generation of superoxide (O 2 Ϫ ). Large deficiencies of endothelial NO synthase (eNOS) mRNA and protein as well as basal and stimulated NO production were observed in aortic endothelial cells 1 and cardiac microvessels 2 from conscious dogs with pacing-induced overt congestive heart failure (CHF). In the same animal model at the onset of cardiac decompensation, reduced basal cardiac NO production was associated with a fall of cardiac contractility and an elevated left ventricular end-diastolic pressure. 3 Similarly, impaired basal and stimulated NO productions, which were indirectly assessed by vascular cyclic GMP, were demonstrated in aortas 4 and pulmonary arteries 4,5 from Wistar-Kyoto rats (WKY) with chronic HF after myocardial infarction (MI). In comparison, a normal acetylcholine-induced relaxation with reduction of basal NO release was found in small mesenteric arteries from this rat HF model. 6,7 Conflicting data exist with regard to eNOS expression and activity in human beings with chronic HF. Increased cardiac express...

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Endothelium-Dependent Relaxation Is Not Uniformly Impaired in Chronic Heart Failure

Cited by 33 publications

References 14 publications

Differences in Tail Vascular Bed Reactivity in Rats with and without Heart Failure following Myocardial Infarction

Differences in Tail Vascular Bed Reactivity in Rats with and without Heart Failure following Myocardial Infarction

Nitric oxide production is maintained in exercising swine with chronic left ventricular dysfunction

Decreased Nitric Oxide Availability in Normotensive and Hypertensive Rats With Failing Hearts After Myocardial Infarction

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