Renal actions of atrial natriuretic peptide in spontaneously hypertensive rats: the role of nitric oxide as a key mediator

Elesgaray, Rosana; Caniffi, Carolina; Savignano, L.; Romero, Mariana; Laughlin, Mark; Arranz, Cristina; Costa, María A.

doi:10.1152/ajprenal.00624.2011

Cited by 6 publications

(6 citation statements)

References 35 publications

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“…In previous studies we demonstrated that male SHR showed increased urinary excretion of NO metabolites and augmented activity of cardiovascular and renal NOS compared to normotensive animals, indicating that the NO pathway is up-regulated in this model of hypertension [15], [33]. In the present study, we showed that female SHR exhibit lower SBP than male SHR.…”

Section: Discussionsupporting

confidence: 68%

Sex Differences in the Beneficial Cardiac Effects of Chronic Treatment with Atrial Natriuretic Peptide In Spontaneously Hypertensive Rats

Romero¹,

Caniffi²,

Bouchet³

et al. 2013

PLoS ONE

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IntroductionThe aim of this study was to investigate both the effects of chronic treatment with atrial natriuretic peptide (ANP) on systolic blood pressure (SBP), cardiac nitric oxide (NO) system, oxidative stress, hypertrophy, fibrosis and apoptosis in spontaneously hypertensive rats (SHR), and sex-related differences in the response to the treatment.Methods10 week-old male and female SHR were infused with ANP (100 ng/hr/rat) or saline (NaCl 0.9%) for 14 days (subcutaneous osmotic pumps). SBP was recorded and nitrites and nitrates excretion (NOx) were determined. After treatment, NO synthase (NOS) activity, eNOS expression, thiobarbituric acid-reactive substances (TBARS) and glutathione concentration were determined in left ventricle, as well as the activity of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD). Morphological studies in left ventricle were performed in slices stained with hematoxylin-eosin or Sirius red to identify collagen as a fibrosis indicator; immunohistochemistry was employed for identification of transforming growth factor beta; and apoptosis was evaluated by Tunel assay.ResultsFemale SHR showed lower SBP, higher NO-system activity and less oxidative stress, fibrosis and hypertrophy in left ventricle, as well as higher cardiac NOS activity, eNOS protein content and NOx excretion than male SHR. Although ANP treatment lowered blood pressure and increased NOS activity and eNOS expression in both sexes, cardiac NOS response to ANP was more marked in females. In left ventricle, ANP reduced TBARS and increased glutathione concentration and activity of CAT and SOD enzymes in both sexes, as well as GPx activity in males. ANP decreased fibrosis and apoptosis in hearts from male and female SHR but females showed less end-organ damage in heart. Chronic ANP treatment would ameliorate hypertension and end-organ damage in heart by reducing oxidative stress, increasing NO-system activity, and diminishing fibrosis and hypertrophy.

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Section: Discussionsupporting

confidence: 68%

Sex Differences in the Beneficial Cardiac Effects of Chronic Treatment with Atrial Natriuretic Peptide In Spontaneously Hypertensive Rats

Romero¹,

Caniffi²,

Bouchet³

et al. 2013

PLoS ONE

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“…37,38,44,45 In addition, NPR-C activation by C-ANP 4-23 was also reported to activate eNOS in various tissues including smooth muscle. 33 We also examined whether C-ANP 4-23 -induced attenuation of BP in SHRs is attributed to its ability to augment the levels of eNOS and NO; however, in the present in vivo study, we demonstrate that C-ANP 4-23 treatment decreased the enhanced levels of NO and eNOS in kidney and attenuated further the decreased levels of eNOS and NO in VSMC and aorta from SHRs and suggest that C-ANP 4-23 -induced decreased BP may not involve NO and NO-stimulated cGMP pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Our results are in accordance with the studies of other investigators who have demonstrated an enhanced expression of iNOS (inducible nitric oxide synthase) and eNOS and an elevation of renal NOS activity in 12-week-old SHRs 52 and 20-week-old SHRs compared with WKY. 53 In addition, Elesgaray et al 38 have shown the overexpression of all the 3 isoforms, eNOS, iNOS, and nNOS (neuronal nitric oxide synthase), in kidney from SHRs compared with WKY rats. Thus taken together, it may be suggested that the upregulation of NOS isoforms in kidney may not contribute to the development of high BP and may play a compensatory role in response to an increased BP in SHRs.…”

Section: Discussionmentioning

confidence: 99%

“…37,38 However, in the present study, we report for the first time that C-ANP [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] that is specific for NPR-C and has no affinity for NPR-A or NPR-B 8,9 attenuated the development of BP in SHRs which is associated with inhibition of enhanced expression of Giα proteins and nitroxidative stress.…”

Section: Discussionmentioning

confidence: 99%

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Natriuretic Peptide Receptor-C Attenuates Hypertension in Spontaneously Hypertensive Rats

Sarkar

Brochu

et al. 2014

Hypertension

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Abstract-C-Atrial natriuretic peptide (ANP) 4-23 , a ring deleted analog of ANP that specifically interacts with natriuretic peptide receptor-C (NPR-C), has been shown to decrease the enhanced expression of Giα proteins implicated in the pathogenesis of hypertension. In the present study, we investigated whether in vivo treatment of spontaneously hypertensive rats (SHRs) with C-ANP 4-23 could attenuate the development of high blood pressure (BP) and explored the underlying mechanisms responsible for this response. Intraperitoneal injection of C-ANP 4-23 at the concentration of 2 or 10 nmol/kg body weight to prehypertensive SHRs attenuated the development of high BP, and at 8 weeks it was decreased by ≈20 and 50 mm Hg, respectively; however, this treatment did not affect BP in Wistar-Kyoto rats. C-ANP 4-23 treatment of adult SHRs for 2 weeks also attenuated high BP, heart rate, and restored the impaired vasorelaxation toward control levels. In addition, the enhanced levels of superoxide anion (O 2 − ), peroxynitrite, NADPH oxidase activity, and the enhanced expression of Giα proteins, NOX4, p47 phox , nitrotyrosine, and decreased levels of endothelial nitric oxide synthase (eNOS or NOS3) and NO in SHRs were attenuated by C-ANP 4-23 treatment; however, the altered levels of NPR-A/NPR-C were not affected by this treatment. In conclusion, these results indicate that NPR-C activation by C-ANP 4-23 attenuates the development of high BP in SHRs through the inhibition of enhanced levels of Giα proteins and nitroxidative stress and not through eNOS/ cGMP pathway and suggest that NPR-C ligand may have the potential to be used as therapeutic agent in the treatment of Li et al NPR-C and Blood Pressure Regulation 847injection of pertussis toxin in prehypertensive rats (2-week-old SHRs) has been reported to prevent the development of BP,22 suggesting the implication of enhanced expression of Gi proteins in the pathogenesis of hypertension. C-ANP 4-23 that specifically interacts with NPR-C has been reported to decrease the levels of Giα proteins in A10 vascular smooth muscle cell (VSMC) 23 and in VSMC from SHRs. 24 In addition, C-ANP 4-23 was also shown to attenuate the enhanced oxidative stress in VSMC from SHRs 24 that contributes to the enhanced expression of Giα proteins in SHRs.25 Taken together, it may be possible that C-ANP 4-23 treatment of SHRs could also attenuate the high BP in SHRs. The present study was undertaken to investigate the effect of in vivo administration of C-ANP 4-23 on the development of high BP in SHRs. We have provided the first evidence that the treatment of prehypertensive SHRs with C-ANP 4-23 , an activator of NPR-C, attenuates the development of high BP in SHRs through the inhibition of enhanced expression of Gi proteins and oxidative stress.We have provided the first evidence that NPR-C activation by C-ANP 4-23 attenuates high BP through decreasing the enhanced oxidative stress and the augmented levels of Giα proteins. From these results it may be suggested that C-ANP [4][5][6][7][8][9][10][...

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“…As expected, chronic treatment with ANP decreased SBP and increased sodium and water excretion. In previous studies we found that these actions of ANP involved, at least in part, an increase in renal NOS activity by interacting with natriuretic receptors NPR-A and NPR-C in both normotensive and hypertensive male animals [33]. …”

Section: Discussionmentioning

confidence: 99%

Chronic Treatment with Atrial Natriuretic Peptide in Spontaneously Hypertensive Rats: Beneficial Renal Effects and Sex Differences

et al. 2015

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ObjectiveThe aim of this study was to investigate the effects of chronic treatment with atrial natriuretic peptide (ANP) on renal function, nitric oxide (NO) system, oxidative stress, collagen content and apoptosis in kidneys of spontaneously hypertensive rats (SHR), as well as sex-related differences in the response to the treatment.Methods10 week-old male and female SHR were infused with ANP (100 ng/h/rat) or saline (NaCl 0.9%) for 14 days (subcutaneous osmotic pumps). Systolic blood pressure (SBP) was recorded and diuresis and natriuresis were determined. After treatment, renal NO synthase (NOS) activity and eNOS expression were evaluated. Thiobarbituric acid-reactive substances (TBARS), glutathione concentration and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were determined in the kidney. Collagen was identified in renal slices by Sirius red staining and apoptosis by Tunel assay.ResultsFemale SHR showed lower SBP, oxidative stress, collagen content and apoptosis in kidney, and higher renal NOS activity and eNOS protein content, than males. ANP lowered SBP, increased diuresis, natriuresis, renal NOS activity and eNOS expression in both sexes. Renal response to ANP was more marked in females than in males. In kidney, ANP reduced TBARS, renal collagen content and apoptosis, and increased glutathione concentration and activity of GPx and SOD enzymes in both sexes.ConclusionsFemale SHR exhibited less organ damage than males. Chronic ANP treatment would ameliorate hypertension and end-organ damage in the kidney by reducing oxidative stress, increasing NO-system activity, and diminishing collagen content and apoptosis, in both sexes.

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Renal actions of atrial natriuretic peptide in spontaneously hypertensive rats: the role of nitric oxide as a key mediator

Cited by 6 publications

References 35 publications

Sex Differences in the Beneficial Cardiac Effects of Chronic Treatment with Atrial Natriuretic Peptide In Spontaneously Hypertensive Rats

Sex Differences in the Beneficial Cardiac Effects of Chronic Treatment with Atrial Natriuretic Peptide In Spontaneously Hypertensive Rats

Natriuretic Peptide Receptor-C Attenuates Hypertension in Spontaneously Hypertensive Rats

Chronic Treatment with Atrial Natriuretic Peptide in Spontaneously Hypertensive Rats: Beneficial Renal Effects and Sex Differences

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