Long-term angiotensin II inhibition increases mitochondrial nitric oxide synthase and not antioxidant enzyme activities in rat heart

Costa, Lidia E.; La-Padula, Pablo; Lores‐Arnaiz, Silvia; D’Amico, Gabriela; Boveris, Alberto; Kurnjek, María L.; Basso, Nidia

doi:10.1097/00004872-200212000-00029

Cited by 54 publications

(44 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results confirmed a protective effect on cardiovascular damage due to aging exerted through inhibition of ANG II and clearly related to diminished ROS (10).…”

Section: Discussionsupporting

confidence: 79%

“…In this sense, earlier data (4,17) have confirmed that nitric oxide synthase (NOS) activity in the aorta and nitric oxide (NO) production diminish with age, whereas chronic long-term administration of angiotensin II (ANG II) inhibitors maintains endothelial NOS activity in old animals. Moreover, the mitochondria from hearts of aged rats chronically treated with ANG II inhibitors were found to have increased NOS activity and decreased hydrogen peroxide formation compared with controls (10).…”

mentioning

confidence: 91%

See 1 more Smart Citation

Protective effect of long-term angiotensin II inhibition

Basso¹,

Cini²,

Pietrelli³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

153

113

View full text Add to dashboard Cite

Experimental studies indicate that angiotensin II (ANG II) through its type 1 receptor (AT1) promotes cardiovascular hypertrophy and fibrosis. Therefore, the aim of this study was to analyze whether chronic long-term inhibition of the renin-angiotensin system (RAS) can prevent most of the deleterious effects due to aging in the cardiovascular system of the normal rat. The main objective was to compare two strategies of ANG II blockade: a converting enzyme inhibitor (CEI) and an AT1 receptor blocker (AT1RB). A control group remained untreated; treatment was initiated 2 wk after weaning. A CEI, enalapril (10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ), or an AT 1RB, losartan (30 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ), was used to inhibit the RAS. Systolic blood pressure, body weight, and water and food intake were recorded over the whole experimental period. Heart, aorta, and mesenteric artery weight as well as histological analysis of cardiovascular structure were performed at 6 and 18 mo. Twenty animals in each of the three experimental groups were allowed to die spontaneously. The results demonstrated a significant protective effect on the function and structure of the cardiovascular system in all treated animals. Changes observed at 18 mo of age in the hearts and aortas were quite significant, but each treatment completely abolished this deterioration. The similarity between the results detected with either enalapril or losartan treatment clearly indicates that most of the effects are exerted through AT 1 receptors. An outstanding finding was the significant and similar prolongation of life span in both groups of treated animals compared with untreated control animals. losartan; enalapril; heart; aorta; life span THE NATURAL PROCESS OF AGING is related to a progressive modification, and ultimately, a loss of organ function. These alterations are common to all species. In general, there is a correlation between the structural and functional changes associated with aging. In mammals, degenerative processes such as arteriosclerosis, the development of senile plaques in the brain, and the replacement of functional parenchyma by fibroconnective tissue in a variety of organs are considered manifestations of aging (19,41).Ultrastructurally, a reduction in the number of cellular organelles such as mitochondria is common in the aging process (13,21,36). Lifelong free radical production could play a main role in the reduction of the number and in both structural and functional mitochondria modifications (6,20,38). It has been widely postulated that reactive oxygen species (ROS) are causally involved in the aging process (19,20). In this sense, earlier data (4, 17) have confirmed that nitric oxide synthase (NOS) activity in the aorta and nitric oxide (NO) production diminish with age, whereas chronic long-term administration of angiotensin II (ANG II) inhibitors maintains endothelial NOS activity in old animals. Moreover, the mitochondria from hearts of aged rats chronically treated with ANG II inhibitors were found to have increased NOS activity and decrease...

show abstract

“…These results confirmed a protective effect on cardiovascular damage due to aging exerted through inhibition of ANG II and clearly related to diminished ROS (10).…”

Section: Discussionsupporting

confidence: 79%

mentioning

confidence: 91%

Protective effect of long-term angiotensin II inhibition

Basso¹,

Cini²,

Pietrelli³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

153

113

View full text Add to dashboard Cite

show abstract

“…Also, the modulation of heart and liver mitochondrial NOS activity and H 2 O 2 production by the ACE inhibitor enalapril has been observed in rats (38,87). Moreover, the expression of genes related to fatty acid ␤-oxidation, mitochondrial protonelectron coupling, and oxidative phosphorylation was upregulated in captopril-treated diabetic animals, suggesting that RAS inhibition with ACE inhibitors may protect the myocardium by enhancing energy supply (75).…”

Section: The Renin-angiotensin Systemmentioning

confidence: 99%

Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition

Cavanagh

Inserra

Ferder

2015

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

de Cavanagh EM, Inserra F, Ferder L. Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition. Am J Physiol Heart Circ Physiol 309: H15-H44, 2015. First published May 1, 2015; doi:10.1152/ajpheart.00459.2014, renin angiotensin system blockade (RAS-bl), and rapamycin-mediated mechanistic target of rapamycin (mTOR) inhibition increase survival and retard aging across species. Previously, we have summarized CR and RAS-bl's converging effects, and the mitochondrial function changes associated with their physiological benefits. mTOR inhibition and enhanced sirtuin and KLOTHO signaling contribute to the benefits of CR in aging. mTORC1/mTORC2 complexes contribute to cell growth and metabolic regulation. Prolonged mTORC1 activation may lead to age-related disease progression; thus, rapamycin-mediated mTOR inhibition and CR may extend lifespan and retard aging through mTORC1 interference. Sirtuins by deacetylating histone and transcription-related proteins modulate signaling and survival pathways and mitochondrial functioning. CR regulates several mammalian sirtuins favoring their role in aging regulation. KLOTHO/fibroblast growth factor 23 (FGF23) contribute to control Ca 2ϩ , phosphate, and vitamin D metabolism, and their dysregulation may participate in age-related disease. Here we review how mTOR inhibition extends lifespan, how KLOTHO functions as an aging suppressor, how sirtuins mediate longevity, how vitamin D loss may contribute to age-related disease, and how they relate to mitochondrial function. Also, we discuss how RAS-bl downregulates mTOR and upregulates KLOTHO, sirtuin, and vitamin D receptor expression, suggesting that at least some of RAS-bl benefits in aging are mediated through the modulation of mTOR, KLOTHO, and sirtuin expression and vitamin D signaling, paralleling CR actions in age retardation. Concluding, the available evidence endorses the idea that RAS-bl is among the interventions that may turn out to provide relief to the spreading issue of age-associated chronic disease. mechanistic target of rapamycin; vitamin D; caloric restriction; renin-angiotensin system EFFORTS AIMED AT DECIPHERING the mechanisms that underlie the aging process have unveiled three interventions that can increase survival and retard age-related diseases from lower organisms to mammals, i.e., caloric restriction (CR) (84,85,140,160,334), mechanistic target of rapamycin (mTOR; originally mammalian TOR) inhibition by rapamycin (173,196,281), and renin-angiotensin system blockade (RAS-bl) (20, 21, 26,63,253,284,354), although the latter has been less studied. In light of these findings, some intriguing questions come to mind: Do these interventions attenuate aging by interfering with common mechanisms? Do the mechanisms that are interfered with by CR, rapamycin, and RAS-bl mutually affect each other? Are there any pathways involved exclusively with a certain intervention?Previously (101), we have discussed the converging effects d...

show abstract

“…2C). Studies of cardiac mtNOS have used various methods including immunohistochemistry (10,66), spectrophotometry (16,30,45,79,115,141,142), radiometry (139,143), fluorometry (40,139,143,147), chemiluminescence (143), and electrochemistry (72). On the other hand, one study reported that the ubiquinone/cyt bc 1 is a site where nitrite is reduced to form NO congeners within mitochondria in a NOS-independent manner (100).…”

Section: Heart Nossmentioning

confidence: 99%

Strategic localization of heart mitochondrial NOS: a review of the evidence

Zaobornyj

Ghafourifar²

2012

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

chondria play a central role in cell energy provision and in signaling. Nitric oxide (NO) is a free radical with primary regulatory functions in the heart and involved in a broad array of key processes in cardiac metabolism. Specific NO synthase (NOS) isoforms are confined to distinct locations in cardiomyocytes. The present article reviews the chemical reactions through which NO interacts with biomolecules and exerts some of its crucial roles. Specifically, the article discusses the reactions of NO with mitochondrial targets and the subcellular localization of NOS within the myocardium and analyzes the available data about heart mitochondrial NOS activity and identity. The article also describes the regulation of heart mtNOS by the distinctive mitochondrial environment by showing the effects of Ca 2ϩ , O2, L-arginine, mitochondrial transmembrane potential, and the metabolic states on heart mitochondrial NO production. The article depicts the effects of NO on heart function and highlights the relevance of NO production within mitochondria. Finally, the evidence on the functional implications of heart mitochondrial NOS is delineated with emphasis on chronic hypoxia and ischemia-reperfusion studies. mitochondrial nitric oxide synthase; calcium; transmembrane potential; hypoxia; ischemia-reperfusion SINCE THE RECOGNITION OF MITOCHONDRIA as the powerhouses of the cells, numerous studies have shown that these organelles play a central role in various biological processes. Under physiological conditions, mitochondria provide the cell with both the energy and the signals involved in the genetic expression and metabolic regulation (35). About two decades ago, the discovery that nitric oxide (NO) is the endothelium-derived relaxing factor caused a paradigm shift in the understanding of cardiovascular physiology and pathophysiology (68,102). NO is a gaseous uncharged 30-Da molecule. It is highly diffusible in aqueous and lipid phases and possesses a biochemistry that supports its role as one of the most versatile molecules in various biological regulatory and signaling processes (76,86,134).In the cardiovascular system, NO plays integral roles not only in the regulation of vascular smooth muscle tone but also in the function of ion channels, myocyte contraction, O 2 consumption, apoptosis, and hypertrophic myocardial remodeling (36, 92). In cardiac endothelial cells and myocytes, NO is generated by NO synthase (NOS) isozymes: neuronal NOS (nNOS or NOS1), inducible NOS (iNOS or NOS2), and endothelial NOS (eNOS or NOS3) (71, 75). Initially, eNOS was considered to be the only isoform constitutively expressed in myocytes and thus the source of NO involved in the autocrine regulation of myocardial contraction and Ca 2ϩ homeostasis (7, 37). However, subsequent studies showed that NOS is targeted to the cardiac sarcoplasmic reticulum (SR) (137) and localized in cardiac mitochondria (72). Additionally, iNOS has been shown to be expressed in the myocardium upon induction by cytokines (8) during inflammatory responses implicated in...

show abstract

Long-term angiotensin II inhibition increases mitochondrial nitric oxide synthase and not antioxidant enzyme activities in rat heart

Cited by 54 publications

References 32 publications

Protective effect of long-term angiotensin II inhibition

Protective effect of long-term angiotensin II inhibition

Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition

Strategic localization of heart mitochondrial NOS: a review of the evidence

Contact Info

Product

Resources

About