ACE Inhibitors Promote Nitric Oxide Accumulation to Modulate Myocardial Oxygen Consumption

Zhang, Xiaoping; Xie, Yi-Wu; Nasjletti, Alberto; Xü, Xinsheng; Wolin, Michael S.; Hintze, Thomas H.

doi:10.1161/01.cir.95.1.176

Cited by 173 publications

(93 citation statements)

References 37 publications

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“…Studies by Hintze et al have shown that endothelium-derived NO reduces myocardial O 2 consumption and influences substrate utilization, the net effect being an increase in cardiac efficiency. 2,14,32 These investigators recently also reported that in canine pacinginduced heart failure, development of decompensated heart failure was accompanied by a reduction in total cardiac NO x production, a switch in myocardial substrate utilization from free fatty acids to glucose, a decrease in cardiac efficiency, and diastolic dysfunction. 32 Whether the same applies in pressure-overload LVH merits investigation.…”

Section: Discussionmentioning

confidence: 96%

Impaired Endothelium-Dependent Regulation of Ventricular Relaxation in Pressure-Overload Cardiac Hypertrophy

MacCarthy

Shah

2000

Circulation

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Background-Endothelium-derived nitric oxide (NO) selectively enhances myocardial relaxation and may benefit diastolic function. Left ventricular hypertrophy (LVH) is characterized by abnormal myocardial relaxation and endothelial dysfunction. We investigated endothelium-dependent regulation of LV relaxation in moderate pressureoverload LVH induced by aortic banding in guinea pigs. Methods and Results-Isolated ejecting hearts of banded or sham-operated animals (shams) were studied. The specific agonists for endothelial release of NO, bradykinin (10 nmol/L), and substance P (100 nmol/L) both induced earlier onset of LV relaxation in shams (time to LV dP/dt min [tdP/dt min ], Ϫ13.4Ϯ3.0 and Ϫ10.4Ϯ2.5 ms, respectively) without altering peak LV pressure or LV dP/dt max . Neither agent altered tdP/dt min in banded animals. The ACE inhibitor captopril (1 mol/L) also selectively reduced tdP/dt min in shams via a bradykinin/NO-dependent mechanism but had no effect in banded animals. An exogenous NO donor, sodium nitroprusside (0.1 mol/L), selectively reduced tdP/dt min to a similar extent in both shams and banded animals. Endothelial-type NO synthase (eNOS) protein expression in whole LV homogenate was unaltered in banded animals. Conclusions-Endothelium-dependent enhancement of LV relaxation is impaired in moderate pressure-overload LVH, despite a preserved response to exogenous NO. This is not accounted for by altered eNOS expression. These abnormalities may contribute to diastolic dysfunction in

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Section: Discussionmentioning

confidence: 96%

Impaired Endothelium-Dependent Regulation of Ventricular Relaxation in Pressure-Overload Cardiac Hypertrophy

MacCarthy

Shah

2000

Circulation

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“…*PϽ0.05, **PϽ0.01. ACE inhibition has previously been shown to promote NO accumulation in coronary microvessels, 31 and certain salutary effects of ACE inhibitors on vasomotor reactivity have been linked to augmented NO release. [32][33][34] Moreover, NO may completely abrogate the caspace cascade activated by Ang II and shown by Dimmeler et al 35 to induce apoptosis of human umbilical vein ECs.…”

Section: Discussionmentioning

confidence: 99%

Tissue Inhibition of Angiotensin-Converting Enzyme Activity Stimulates Angiogenesis In Vivo

et al. 1999

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Background-Endothelial cells (ECs) represent the critical cellular element responsible for postnatal angiogenesis.Because ACE inhibitors may favorably affect endothelial function, we investigated the hypothesis that administration of the ACE inhibitor quinaprilat could enhance angiogenesis in vivo. Methods and Results-Ten days after resection of 1 femoral artery, New Zealand White (NZW) rabbits were randomly assigned to receive recombinant human vascular endothelial growth factor (rhVEGF) administered as a single intra-arterial injection (nϭ6), quinaprilat (nϭ8) or captopril (nϭ7) administered as a daily subcutaneous injection, or no treatment (controls, nϭ6). Angiogenesis was monitored in vivo by measurement of blood pressure, vasoreactivity, and resistance in ischemic versus normal limbs at day 10 (D10) and D40; angiographic studies to identify sites of neovascularization were performed at D10 and D40, and morphometric analysis of capillary density in the ischemic limb was performed at necropsy (D40). Both functional and morphological outcomes documented augmented angiogenesis in quinaprilat-treated rabbits similar to that observed for rhVEGF and superior to that observed with either captopril or no drug (controls). Residual ACE activity was equivalent for the captopril and quinaprilat groups in plasma (42.54Ϯ0.03% versus 41.53Ϯ0.02%, PϭNS) but not in tissue, where quinaprilat lowered ACE activity significantly (PϽ0.01) compared with captopril (13% versus 61%). Conclusions-ACE inhibition with quinaprilat promotes angiogenesis in a rabbit model of hindlimb ischemia. Thus, nonsulfhydryl ACE inhibitors with high tissue affinity may be potentially useful for therapeutic angiogenesis in ischemic tissues. Moreover, previous evidence that ACE inhibition benefits patients with myocardial ischemia may be due in part to augmented collateral development. (Circulation. 1999;99:3043-3049.)

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“…This idea is supported by studies in myocardial tissue demonstrating that oxidative metabolism and myocardial performance is dependent on a balanced ACE activity. 75,198 Further investigations in this area are clearly required to more thoroughly evaluate this concept. …”

Section: Perspectivesmentioning

confidence: 99%

Review: Angiotensin-converting enzyme in skeletal muscle: sentinel of blood pressure control and glucose homeostasis

Dietze¹,

Henriksen

2008

J Renin Angiotensin Aldosterone Syst

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Recent evidence suggests a coordinated regulation by the local renin-angiotensin system (RAS) and tissue kallikrein-kinin system (TKKS) of blood flow and substrate supply in oxidative red myofibres of skeletal muscle tissue during endurance exercise.The performance of these myofibres is dependent on the increased oxidation of substrates facilitated by augmenting nutritive blood flow and glucose uptake. Humoral factors released by the contracting fibres, such as adenosine and kinins, are suggested to be responsible for this metabolic adjustment.The considerable drain of blood volume and the enormous consumption of glucose during endurance exercise require a control mechanism for the maintenance of blood pressure (BP) and glucose homeostasis. This is achieved by the sympathetic nervous system and its subordinate RAS, which is located in the nutritive vessels and parenchyma of the red myofibres. The angiotensin-converting enzyme (ACE) is the primary enzyme responsible for kinin degradation during exercise, underscoring the important interrelationship between the RAS and the TKKS in the critical role of kinins in the multifactorial regulation of muscle bioenergetics and glucose and BP homeostasis. Importantly, overactivity of the ACE, as occurs in individuals displaying risk factors such as overweight, causes exaggerated BP response and reduced glucose disposal. If they persist over years, compensatory responses to this ACE overactivity, such as hypersecretion of insulin and compliance of the vessel walls, will inevitably be exhausted, leading ultimately to the manifestation of type 2 diabetes and hypertension. This concept also provides a unifying explanation for the beneficial effects of ACE-inhibitors and Angiotensin II receptor antagonists in the treatment of hypertension and insulin resistance.Need for control of blood pressure and glucose homeostasis during endurance exercise performance The regulation of muscle bioenergetics during exercise has been studied for more than 100 years.

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ACE Inhibitors Promote Nitric Oxide Accumulation to Modulate Myocardial Oxygen Consumption

Cited by 173 publications

References 37 publications

Impaired Endothelium-Dependent Regulation of Ventricular Relaxation in Pressure-Overload Cardiac Hypertrophy

Impaired Endothelium-Dependent Regulation of Ventricular Relaxation in Pressure-Overload Cardiac Hypertrophy

Tissue Inhibition of Angiotensin-Converting Enzyme Activity Stimulates Angiogenesis In Vivo

Review: Angiotensin-converting enzyme in skeletal muscle: sentinel of blood pressure control and glucose homeostasis

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