Angiotensin converting enzyme inhibitors: spirapril and related compounds

Smith, Elizabeth M.; Swiss, Gerald F.; Neustadt, Bernard R.; McNamara, Paul E.; Gold, Elijah H.; Sybertz, Edmund J.; Baum, Thomas

doi:10.1021/jm00127a033

Cited by 41 publications

(14 citation statements)

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“…Resting MABP was recorded over 15 min before and 20 min after blockade of endogenous ANG II formation by angiotensin-converting enzyme inhibitor enalaprilat (150 g/kg iv) (69 Ex vivo vascular reactivity studies. Freshly excised carotid arteries from anesthetized offspring were placed in ice-cold modified Krebs bicarbonate solution of the following composition (in mM): 118 NaCl, 4.7 KCl, 25 NaHCO 3, 2.5 CaCl2, 1.2 MgSO4, 1.2 KH2PO4, and 11 dextrose.…”

Section: Methodsmentioning

confidence: 99%

Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet

Cambonie¹,

Comte²,

Yzydorczyk³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

151

158

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Nuyt AM. Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet. Am J Physiol Regul Integr Comp Physiol 292: R1236 -R1245, 2007. First published November 30, 2006; doi:10.1152/ajpregu.00227.2006.-Developmental programming of hypertension is associated with vascular dysfunction characterized by impaired vasodilatation to nitric oxide, exaggerated vasoconstriction to ANG II, and microvascular rarefaction appearing in the neonatal period. Hypertensive adults have indices of increased oxidative stress, and newborns that were nutrient depleted during fetal life have decreased antioxidant defenses and increased susceptibility to oxidant injury. To test the hypothesis that oxidative stress participates in early life programming of hypertension, vascular dysfunction, and microvascular rarefaction associated with maternal protein deprivation, pregnant rats were fed a normal, low protein (LP), or LP plus lazaroid (lipid peroxidation inhibitor) isocaloric diet from the day of conception until delivery. Lazaroid administered along with the LP diet prevented blood pressure elevation, enhanced vasomotor response to ANG II, impaired vasodilatation to sodium nitroprusside, and microvascular rarefaction in adult offspring. Liver total glutathione was significantly decreased in LP fetuses, and kidney eight-isoprostaglandin F2␣ (8-isoPGF 2␣) levels were significantly increased in adult LP offspring; these modifications were prevented by lazaroid. Renal nitrotyrosine abundance and blood levels of 1,4-dihydroxynonene and 4-hydroxynonenal-protein adducts were not modified by antenatal diet exposure. This study shows in adult offspring of LP-fed dams prevention of hypertension, vascular dysfunction, microvascular rarefaction, and of an increase in indices of oxidative stress by the administration of lazaroid during gestation. Lazaroid also prevented the decrease in antioxidant glutathione levels in fetuses, suggesting an antenatal mild oxidative stress in offspring of LP-fed dams. These studies support the concept that perinatal oxidative insult can lead to permanent alterations in the cardiovascular system development.hypertension; vascular dysfunction; developmental origin of adult disease; oxidative stress; antioxidants.Cardiovascular diseases represent currently the leading cause of mortality in Western countries. The hypothesis of a developmental origin of these pathologies derives from epidemiological studies, indicating that, independent of genetic or life style factors, the risks of hypertension (HT), stroke, and coronary heart disease in later life are inversely proportional to birth weight. Alteration of the vascular response to ACh, a decreased arterial compliance, and an increased incidence of atherosclerosis are all evidence further illustrating the vascular risk in children and adults born with low birth weight and/or intrauterine growth retardation (3,4,44,47).Experimentally, HT is observed in adults after malnutrit...

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Section: Methodsmentioning

confidence: 99%

Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet

Cambonie¹,

Comte²,

Yzydorczyk³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

151

158

View full text Add to dashboard Cite

show abstract

“…In LP and CTRL offspring, resting MABP was recorded for a period of 15 min before and 20 min after blockade of endogenous ANG II formation by the angiotensin-converting enzyme inhibitor enalaprilat (150 g/kg iv) (61). MABP responses to continuous intravenous infusions of ANG II (10, 20, and 40 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ), phenylephrine (20 and 40 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) or NO donor sodium nitroprusside (SNP; 10, 20, and 40 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) were then determined.…”

Section: Methodsmentioning

confidence: 99%

Microvascular rarefaction and decreased angiogenesis in rats with fetal programming of hypertension associated with exposure to a low-protein diet in utero

Pladys¹,

Sennlaub²,

Brault³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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In hypertension, increased peripheral vascular resistance results from vascular dysfunction with or without structural changes (vessel wall remodeling and/or microvascular rarefaction). Humans with lower birth weight exhibit evidence of vascular dysfunction. The current studies were undertaken to investigate whether in utero programming of hypertension is associated with in vivo altered response and/or abnormal vascular structure. Offspring of Wistar dams fed a normal (CTRL) or low (LP)-protein diet during gestation were studied. Mean arterial blood pressure response to ANG II was significantly increased, and depressor response to sodium nitroprusside (SNP) infusions significantly decreased in male LP adult offspring relative to CTRL. No arterial remodeling was observed in male LP compared with CTRL offspring. Capillary and arteriolar density was significantly decreased in striated muscles from LP offspring at 7 and 28 days of life but was not different in late fetal life [day 21 of gestation (E21)]. Angiogenic potential of aortic rings from LP newborn (day of birth, P0) was significantly decreased. Striated muscle expressions (Western blots) of ANG II AT(1) receptor subtype, endothelial nitric oxide synthase, angiopoietin 1 and 2, Tie 2 receptor, vascular endothelial growth factor and receptor, and platelet-derived growth factor C at E21 and P7 were unaltered by antenatal diet exposure. In conclusion, blood pressure responses to ANG II and SNP are altered, and microvascular structural changes prevail in this model of fetal programming of hypertension. The capillary rarefaction is absent in the fetus and appears in the neonatal period, in association with decreased angiogenic potential. The study suggests that intrauterine protein restriction increases susceptibility to postnatal factors resulting in microvascular rarefaction, which could represent a primary event in the genesis of hypertension.

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“…Many of the fused pyridine compounds have been proven as valuable candidates possessing anti-bacterial (Elagamey, Sattar, El-Taweel, & Said, 2015), anti-fungal (Hanafy, 2011), anti-microbial (Paresh & Yogesh, 2015), antioxidant (Farghaly, Abass, Abdalla, & Mahgoub, 2011;Flefel et al, 2014), anti-cancer (Bladt, Frisvad, Knudsen, & Larsen, | 465 LAVANYA et AL. 2013;Naresh Kumar et al, 2016), anti-psychotic (Swain et al, 1992), anti-inflammatory (Hend, At-Allah, A-Rahman, & El-Gazza, 2008;Piero & Lucio, 2012), anti-leishmanial (Samai, Nandi, Chowdhury, & Singh, 2011), anti-viral (Tai et al, 2014, anti-hypersensitive (Smith et al, 1989), anticonvulsants (Kaminski, Obniska, Zagorska, & Maciag, 2006), anti-malarial (Davoll, Clarke, & Elslage, 1972), potassium channel openers (Gadwood et al, 1993), anti-diabetic (Sarges, Bordner, Dominy, Peterson, & Whipple, 1985) and anti-tumour activities (Mohamed & Giuseppe, 2016). A few of previously reported bio-active fused compounds (A-D) were represented in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

One pot multi‐component synthesis of functionalized spiropyridine and pyrido[2,3‐d]pyrimidine scaffolds and their potent in‐vitro anti‐inflammatory and anti‐oxidant investigations

2018

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A new series of functionalized fused pyridines 4(a–i) and fused pyrido[2,3‐d]pyrimidines 8(a–c) were designed and synthesized through a multi‐component reaction where in pyridine ring formation step plays a key role. All the newly formed compounds were well characterized by spectral techniques such as FTIR, 1HNMR, 13CNMR, HRMS and XRD. The potential therapeutic activities such as anti‐inflammatory activity by protein denaturation and RBC membrane stabilization methods, and anti‐oxidant activity by DPPH scavenging method of the newly synthesized compounds were studied. Interestingly, in‐vitro testing of these compounds reveals that the compounds 4d, 4g, 4i, 8a and 8b showed comparable anti‐inflammatory activity with respect to the standard drug, diclofenac. Similarly, fused pyridine 4f showed excellent anti‐oxidant activity when compared with the standard, ascorbic acid.

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Angiotensin converting enzyme inhibitors: spirapril and related compounds

Cited by 41 publications

References 0 publications

Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet

Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet

Microvascular rarefaction and decreased angiogenesis in rats with fetal programming of hypertension associated with exposure to a low-protein diet in utero

One pot multi‐component synthesis of functionalized spiropyridine and pyrido[2,3‐d]pyrimidine scaffolds and their potent in‐vitro anti‐inflammatory and anti‐oxidant investigations

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