The PI3K–Akt–eNOS pathway is involved in aortic hyporeactivity to Phenylephrine associated with late pregnancy in spontaneously hypertensive rats

Zancheta, Dalise; Troiano, Jéssica A.; Potje, Simone R.; Cavalari, Priscila; Sumida, Dóris Hissako; Antoniali, Cristina

doi:10.1016/j.lfs.2014.12.014

Cited by 12 publications

(8 citation statements)

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“…We observed greater amount of NO in the aorta and mesenteric bed at the end of pregnancy, as indirectly measured by nitrite levels (Figures 1A,B). This increase in NO may be associated with increased total eNOS and p-eNOS Ser1177 expression in the aorta and higher NO concentration in aortic endothelial cells from P Wistar rats and P SHR, as already observed by our research team (Zancheta et al, 2015;Troiano et al, 2016). Moreover, in the aorta, where NO is the main regulatory factor of vascular homeostasis, variation of NO levels is greater in NP SHR and P SHR than in NP Wistar rats and P Wistar rats, emphasizing the importance of this molecule for regulation of vascular mechanisms during pregnancy of hypertensive rats.…”

Section: Discussionsupporting

confidence: 81%

“…Pregnancy in normotensive Wistar rats and spontaneously hypertensive rats (SHR) is a physiological process characterized by significant reduction in mean arterial pressure despite increased plasma volume. This phenomenon stems from reduced peripheral vascular resistance associated with decreased pressor responses and reduced contractile response to vasoconstrictors ( Barron et al, 1984 ; Chu and Beilin, 1993a , b ; Ballejo et al, 2002 ; Elias et al, 2008 ; Stennett et al, 2009 ; Ognibene et al, 2012 ; Zancheta et al, 2015 ; Troiano et al, 2016 ). Compared to blood vessels from non-pregnant rats, eNOS activity is increased in systemic arteries from late pregnant normotensive and hypertensive rats.…”

Section: Introductionmentioning

confidence: 99%

“…Compared to blood vessels from non-pregnant rats, eNOS activity is increased in systemic arteries from late pregnant normotensive and hypertensive rats. Increased eNOS activity, and hence greater NO production, negatively modulates contraction of systemic blood vessels during pregnancy ( Zancheta et al, 2015 ; Troiano et al, 2016 ). In this study, we hypothesized that pregnancy changes cell signaling involving caveolae, Cav-1, CaM, Hsp90, and eNOS in arteries from normotensive and SHR.…”

Section: Introductionmentioning

confidence: 99%

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Caveolin-1/Endothelial Nitric Oxide Synthase Interaction Is Reduced in Arteries From Pregnant Spontaneously Hypertensive Rats

et al. 2021

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We have investigated the role caveolae/caveolin-1 (Cav-1) plays in endothelial nitric oxide synthase (eNOS) activation and how it impacts pregnancy-induced decreased vascular reactivity in normotensive (Wistar rats) and spontaneously hypertensive rats (SHR). Wistar rats and SHR were divided into non-pregnant (NP) and pregnant (P). Nitrite levels were assessed by the Griess method in the aorta and mesenteric vascular bed. In functional studies, arteries were incubated with methyl-β-cyclodextrin (dextrin, 10mmol/L), which disrupts caveolae by depleting cholesterol, and concentration-response curves to phenylephrine (PE) and acetylcholine (ACh) were constructed. Electronic microscopy was used to determine endothelial caveolae density in the aorta and resistance mesenteric artery in the presence of vehicle or dextrin (10mmol/L). Western blot was performed to evaluate Cav-1, p-Cav-1, calmodulin (CaM), and heat shock protein 90 (Hsp90) expression. Cav-1/eNOS interaction in the aorta and mesenteric vascular bed was assessed by co-immunoprecipitation. Nitric oxide (NO) generation was greater in arteries from P groups compared to NP groups. Dextrin did not change vascular responses in the aorta from P groups or the number of caveolae in P groups compared to NP groups. Compared to NP Wistar rats, NP SHR showed smaller number of caveolae and reduced Cav-1 expression. Pregnancy did not alter Cav-1, CaM, or Hsp90 expression in the aorta or mesenteric vascular bed from Wistar rats or SHR. These results suggest that pregnancy does not alter expression of the main eNOS regulatory proteins, but it decreases Cav-1/eNOS interaction. Reduced Cav-1/eNOS interaction in the aorta and mesenteric vascular bed seems to be an important mechanism to increase eNOS activity and nitric oxide production in pregnant normotensive and hypertensive rats.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Caveolin-1/Endothelial Nitric Oxide Synthase Interaction Is Reduced in Arteries From Pregnant Spontaneously Hypertensive Rats

et al. 2021

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“…Further investigations are required to assess the potential of alprostadil for the treatment of humans with myocardial infarction. Secondly, protein kinase B (Akt) may mediate the phosphorylation of eNOS 25 . Although the downstream target of Akt, eNOS, was examined in the present study, the effect of alprostadil on the expression of Akt requires further investigation.…”

Section: ■ Discussionmentioning

confidence: 99%

Alprostadil attenuates myocardial ischemia/reperfusion injury by promoting antioxidant activity and eNOS activation in rats

Zhang

et al. 2018

Acta Cir. Bras.

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Purpose: To investigate the effect of alprostadil on myocardial ischemia/reperfusion (I/R) in rats. Methods: Rats were subjected to myocardial ischemia for 30 min followed by 24h reperfusion. Alprostadil (4 or 8 μg/kg) was intravenously administered at the time of reperfusion and myocardial infarct size, levels of troponin T, and the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in the serum were measured. Antioxidative parameters, nitric oxide (NO) content and phosphorylated endothelial nitric oxide synthase 3 (p-eNOS) expression in the left ventricles were also measured. Histopathological examinations of the left ventricles were also performed. Results: Alprostadil treatment significantly reduced myocardial infarct size, serum troponin T levels, and CK-MB and LDH activity (P<0.05). Furthermore, treatment with alprostadil significantly decreased malondialdehyde (MDA) content (P<0.05) and markedly reduced myonecrosis, edema and infiltration of inflammatory cells. Superoxide dismutase and catalase activities (P<0.05), NO level (P<0.01) and p-eNOS (P<0.05) were significantly increased in rats treated with alprostadil compared with control rats. Conclusion: These results indicate that alprostadil protects against myocardial I/R injury and that these protective effects are achieved, at least in part, via the promotion of antioxidant activity and activation of eNOS.

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“…No changes have been reported in sensory innervation [ 4 ] but there is an increased vasodilation to CGRP [ 7 , 15 , 16 ]. It is widely known that estrogens modulate vascular tone activating endothelial nitric oxide synthase (eNOS) and several studies have reported that vascular adaptation in pregnancy is associated with an increase in eNOS protein expression [ 17 , 18 , 19 ]. In previous studies we have observed that changes in levels of sex steroids are associated with changes in nitrergic innervation function [ 14 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Alterations in Perivascular Sympathetic and Nitrergic Innervation Function Induced by Late Pregnancy in Rat Mesenteric Arteries

et al. 2015

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Background and PurposeWe investigated whether pregnancy was associated with changed function in components of perivascular mesenteric innervation and the mechanism/s involved.Experimental ApproachWe used superior mesenteric arteries from female Sprague-Dawley rats divided into two groups: control rats (in oestrous phase) and pregnant rats (20 days of pregnancy). Modifications in the vasoconstrictor response to electrical field stimulation (EFS) were analysed in the presence/absence of phentolamine (alpha-adrenoceptor antagonist) or L-NAME (nitric oxide synthase-NOS- non-specific inhibitor). Vasomotor responses to noradrenaline (NA), and to NO donor DEA-NO were studied, NA and NO release measured and neuronal NOS (nNOS) expression/activation analysed.Key ResultsEFS induced a lower frequency-dependent contraction in pregnant than in control rats. Phentolamine decreased EFS-induced vasoconstriction in segments from both experimental groups, but to a greater extent in control rats. EFS-induced vasoconstriction was increased by L-NAME in arteries from both experimental groups. This increase was greater in segments from pregnant rats. Pregnancy decreased NA release while increasing NO release. nNOS expression was not modified but nNOS activation was increased by pregnancy. Pregnancy decreased NA-induced vasoconstriction response and did not modify DEA-NO-induced vasodilation response.Conclusions and ImplicationsNeural control of mesenteric vasomotor tone was altered by pregnancy. Diminished sympathetic and enhanced nitrergic components both contributed to the decreased vasoconstriction response to EFS during pregnancy. All these changes indicate the selective participation of sympathetic and nitrergic innervations in vascular adaptations produced during pregnancy.

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The PI3K–Akt–eNOS pathway is involved in aortic hyporeactivity to Phenylephrine associated with late pregnancy in spontaneously hypertensive rats

Cited by 12 publications

References 29 publications

Caveolin-1/Endothelial Nitric Oxide Synthase Interaction Is Reduced in Arteries From Pregnant Spontaneously Hypertensive Rats

Caveolin-1/Endothelial Nitric Oxide Synthase Interaction Is Reduced in Arteries From Pregnant Spontaneously Hypertensive Rats

Alprostadil attenuates myocardial ischemia/reperfusion injury by promoting antioxidant activity and eNOS activation in rats

Alterations in Perivascular Sympathetic and Nitrergic Innervation Function Induced by Late Pregnancy in Rat Mesenteric Arteries

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