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

Date Published: March 16, 2015

Publisher: Public Library of Science

Author(s): Mariana Romero, Carolina Caniffi, Gonzalo Bouchet, María A. Costa, Rosana Elesgaray, Cristina Arranz, Analía L. Tomat, Christopher Torrens.


The 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.

10 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.

Female 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.

Female 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.

Partial Text

It is well established that blood pressure is higher in men than age-match premenopausal women. However, after menopause, the prevalence of hypertension in women is higher than it is in men [1, 2]. Moreover, progression of hypertensive renal disease tends to be milder in females, with a favorable influence in the physiopathology of hypertension and secondary kidney damage [3, 4].

In the present study we demonstrated that chronic treatment with ANP exerts beneficial effects in kidney of SHR, reducing oxidative stress, collagen content and apoptosis. These actions were also accompanied by an increase in renal NO-system activity. Moreover, we found that important sex differences exist in this model of hypertension and in the response to chronic ANP treatment.

In summary, we have demonstrated that the kidney of female SHR presents less collagen deposit, apoptosis and oxidative stress in this model of hypertension. Taking into account that NO exerts antioxidant and antifibrotic effects [56, 57], along with our previous findings linking ANP and eNOS activation, we can postulate that indirect effects of ANP in kidney would be mediated, at least in part, by the increase in NO, which also contributes to reduce oxidative stress.