The denervation or activation of renal sympathetic nerve and renal blood flow.

The denervation or activation of the sympathetic nerve in the kidney can affect renal hemodynamics. The sympathetic nervous system regulates the physiological functions of the kidneys. Stimulation of sympathetic efferent nerves affects various parameters related to renal hemodynamics, including sodium excretion, renin secretion, and renal blood flow (RBF). Hence, renal sympathetic fibers may also play an essential role in regulating systemic vascular resistance and controlling blood pressure. In the absence of renal nerves, the hemodynamics response to stimuli is negligible or absent. The effect of renal sympathetic denervation on RBF is dependent on several factors such as interspecies differences, the basic level of nerve activity in the vessels or local density of adrenergic receptor in the vascular bed. The role of renal denervation has been investigated therapeutically in hypertension and related disorders. Hence, the dynamic impact of renal nerves on RBF enables using RBF dynamic criteria as a marker for renal denervation therapy.

The role of Mas receptor on renal hemodynamic responses to angiotensin II administration in chronic renal sympathectomized male and female rats.

Background and purpose: Renal hemodynamics is influenced by renal sympathetic nerves and the renin-angiotensin system. On the other hand, renal sympathetic denervation impacts kidney weight by affecting renal hemodynamics. The current study evaluated the role of the Mas receptor on renal hemodynamic responses under basal conditions and in response to angiotensin II (Ang II) in chronic renal sympathectomy in female and male rats. Experimental approach: Forty-eight nephrectomized female and male rats were anesthetized and cannulated. Afterward, the effect of chronic renal sympathectomy was investigated on hemodynamic parameters such as renal vascular resistance (RVR), mean arterial pressure (MAP), and renal blood flow (RBF). In addition, the effect of chronic sympathectomy on kidney weight was examined. Findings/Results: Chronic renal sympathectomy increased RVR and subsequently decreased RBF in both sexes. Renal perfusion pressure also increased after sympathectomy in male and female rats, while MAP did not change, significantly. In response to the Ang II injection, renal sympathectomy caused a greater decrease in RBF in all experimental groups, while it did not affect the MAP response. In addition, chronic sympathectomy increased left kidney weight in right nephrectomized rats. Conclusion and implications: Chronic renal sympathectomy changed systemic/renal hemodynamics in baseline conditions and only renal hemodynamics in response to Ang II administration. Moreover, chronic sympathectomy increased compensatory hypertrophy in nephrectomized rats. These changes are unaffected by gender difference and Mas receptor blocker.

Age- and Gender-Related Differences in Renal Vascular Responses to Angiotensin II in Rats: The Role of the Mas Receptor.

Background: Renal hemodynamic is influenced by both gender difference and age. Also, the Mas receptor (MasR) as one of the depressor components of the renin-angiotensin system which has more expression in females could postpone some dysfunctions associated with age, although the association between MasR and age in renal vascular responses to angiotensin II (Ang II) in male and female rats was well undefined. Therefore, the current study examined the effects of age and sex on systemic and renal vascular responses to graded doses of Ang II in Wistar rats with or without MasR antagonists (A779). Materials and Methods: Anesthetized Wistar male and female rats with two age ranges of 8-12 and 24-28 weeks were exposed to cannulate venous and arterial vessels. After stability, mean arterial pressure (MAP), renal perfusion pressure (RPP), renal vascular resistance (RVR), and renal blood flow (RBF) were measured in response to the infusion of Ang II with or without A779. Results: There were no significant differences in the base values of MAP, RPP, RBF, and RVR between the two genders in both the age ranges of 8-12 and 24-28 weeks. In addition, no significant gender difference was observed in the age ranges of the above mentioned parameters among the groups receiving vehicle or A779. Also, the infusion of vehicle or A779 could not significantly change the base values. On the other hand, the responses of RBF and RVR to Ang II revealed gender differences among 8-12-week groups (P < 0.05) but not in 24-28-week groups, while the blockade of MasR could not influence the responses in the age ranges. Conclusion: It was concluded that age could impress sex difference in RBF and RVR responses to Ang II infusion and that MasR alone could not participate in these responses. In other words, MasR is not active under normal and acutely elevated Ang II levels.

Renal vascular responses to angiotensin II infusion in two kidneys-one clip hypertensive rats under partial ischemia/reperfusion with and without ischemia preconditioning: the roles of AT1R blockade and co-blockades of AT1R and MasR.

Background and purpose: The renin-angiotensin system activation, partial ischemia/reperfusion (IR) injury, and hypertension contribute to the development of acute kidney injury. The study aims to look at the vascular responses of angiotensin II (Ang II) during Ang II type 1 receptor (AT1R) blockade (losartan) or co-blockades of AT1R and Mas receptor (A779) in two kidneys one clip (2K1C) hypertensive rats which subjected to partial IR injury with and without ischemia preconditioning (IPC). Experimental approach: Thirty-three 2K1C male Wistar rats with systolic blood pressure ≥ 150 mmHg were divided into three groups of sham, IR, and IPC + IR divided into two sub-groups receiving losartan or losartan + A779. The IR group had 45 min partial kidney ischemia, while the IPC + IR group had two 5 min cycles of partial ischemia followed by 10 min of reperfusion and then 45 min of partial kidney ischemia followed by reperfusion. The sham group was subjected to similar surgical procedures except for IR or IPC. Findings/Results: Ang II increased mean arterial pressure in all the groups, but there were no significant differences between the sub-groups. A significant difference was observed in the renal blood flow response to Ang II between two sub-groups of sham and IR groups treated with AT1R blockade alone or co-blockades of AT1R + A779. Conclusion and implications: These findings demonstrated the significance of AT1R and Mas receptor following partial renal IR in the renal blood flow responses to Ang II in 2K1C hypertensive rats.

Sodium hydrogen sulfide may not protect the kidney against ischemia/reperfusion damage in male and female rats.

Background and purpose: Renal ischemia/reperfusion (IR) injury is a pathologic phenomenon that caused to increase risk of mortality. The main objective of this study was to investigate the effect of sodium hydrogen sulfide (NaHS) on renal IR injury in male and female rats. Experimental approach: Fifty-eight male and female rats were randomized into 4 groups of control, sham, IR, and IR + NaHS. The IR was performed by 45 min of ischemia by vessel clamping followed by 24 h reperfusion. The NaHS (100 µmol/kg) treatment was applied 10 min prior to IR. Finally, after 24 h of reperfusion, the measurements were performed. Findings/Results: The serum levels of blood urea nitrogen, creatinine, tissue level of malondialdehyde, and kidney tissue damage score (KTDS) were increased by IR. Urine volume, creatinine, and urea clearances decreased by IR. NaHS administration improved some parameters in males but exacerbated KTDS and serum markers related to renal function. Conclusions and implications: Our data demonstrated that NaHS didn't protect female rats against renal IR injury. In males, it has null effects or just a few protective effects via antioxidant activity.

View of the Renin-Angiotensin System in Acute Kidney Injury Induced by Renal Ischemia-Reperfusion Injury.

Renal ischemia-reperfusion injury (RIRI) is a sequence of complicated events that is defined as a reduction of the blood supply followed by reperfusion. RIRI is the leading cause of acute kidney injury (AKI). Among the diverse mediators that take part in RIRI-induced AKI, the renin-angiotensin system (RAS) plays an important role via conventional (angiotensinogen, renin, angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and Ang II type 1 receptor (AT1R)) and nonconventional (ACE2, Ang 1-7, Ang 1-9, AT2 receptor (AT2R), and Mas receptor (MasR)) axes. RIRI alters the balance of both axes so that RAS can affect RIRI-induced AKI. In overall, the alteration of Ang II/AT1R and AKI by RIRI is important to consider. This review has looked for the effects and interactions of RAS activities during RIRI conditions.

Sex Difference in Cisplatin-Induced Nephrotoxicity: Laboratory and Clinical Findings.

Cisplatin (CP) as the most important anticancer drug has limited usage due to a lot of side effects such as nephrotoxicity. Additionally, nephrotoxicity is gender/sex-related. There is a variety of experimental studies in association with sex and CP-induced nephrotoxicity. Some studies have reported that female sex is resistant than male sex due to greater antioxidant defense and protective effects of estrogen in females. Other studies have indicated that males are less vulnerable than females due to CP high clearance. Also, various supplementations have revealed conflicting effects in males and females. It is uncovered that sex hormones have determinant roles on the conflicting effects. Some supplements could improve CP-induced nephrotoxicity, but several supplements intensified CP-induced nephrotoxicity, especially in female sex. On the other hand, major clinical studies introduced female gender as a risk factor of CP-induced nephrotoxicity. Although, rare studies evaluated the effect of various supplemental compounds on CP-induced nephrotoxicity in patients underwent CP therapy. Therefore, it requires further investigations to clarify the controversial subject of gender/sex and CP-induced nephrotoxicity in both clinic and laboratory.

Renal Denervation Influences Angiotensin II Types 1 and 2 Receptors.

The sympathetic and renin-angiotensin systems (RAS) are two critical regulatory systems in the kidney which affect renal hemodynamics and function. These two systems interact with each other so that angiotensin II (Ang II) has the presynaptic effect on the norepinephrine secretion. Another aspect of this interaction is that the sympathetic nervous system affects the function and expression of local RAS receptors, mainly Ang II receptors. Therefore, in many pathological conditions associated with an increased renal sympathetic tone, these receptors' expression changes and renal denervation can normalize these changes and improve the diseases. It seems that the renal sympathectomy can alter Ang II receptors expression and the distribution of RAS receptors in the kidneys, which influence renal functions.

Sex Difference in MasR Expression and Functions in the Renal System.

Renin-angiotensin system (RAS), as a critical system for controlling body fluid and hemostasis, contains peptides and receptors, including angiotensin 1-7 (Ang 1-7) and Mas receptor (MasR). Ang 1-7 implements its function via MasR. Ang II is another peptide in RAS that performs its actions via two Ang II type 1 and 2 receptors (AT1R and AT2R). The functions of AT2R and MasR are very similar, and both have a vasodilation effect, while AT1R has a vasoconstriction role. MasR affects many mechanisms in the brain, heart, blood vessels, kidney, lung, endocrine, reproductive, skeletal muscle, and liver and probably acts like a paracrine hormone in these organs. The effect of Ang 1-7 in the kidney is complex according to the hydroelectrolyte status, the renal sympathetic nervous system, and the activity level of the RAS. The MasR expression and function seem more complex than Ang II receptors and have interacted with Ang II receptors and many other factors, including sex hormones. Also, pathological conditions including hypertension, diabetes, and ischemia-reperfusion could change MasR expression and function. In this review, we consider the role of sex differences in MasR expression and functions in the renal system under physiological and pathological conditions.

Estradiol Supplement or Induced Hypertension May Attenuate the Angiotensin II Type 1 Receptor Antagonist-Promoted Renal Blood Flow Response to Graded Angiotensin II Administration in Ovariectomized Rats.

Backgrounds: Estrogen replacement therapy (ERT) and hypertension may influence females' renin-angiotensin system (RAS) and its components. The angiotensin II (Ang II) type 1 receptor (AT1R) antagonist (losartan) may promote renal blood flow (RBF), and it is widely used in the clinic to control hypertension. The main objective of this study was the effects of estradiol or induced hypertension on RBF response to Ang II in losartan-treated ovariectomized (OVX) rats. Methods: Two groups of OVX rats were treated with placebo (group 1) and estradiol (group 2) for period of four weeks, and another group of OVX rats was subjected to induce hypertension by two-kidney one clip (2K1C) model (group 3). All the groups were subjected to the surgical procedure under anesthesia, and AT1R was blocked by losartan. RBF and renal vascular resistance (RVR) responses to Ang II administration were determined and compared. Results: Mean arterial (MAP) and renal perfusion (RPP) pressures in group 3 and uterus weight (UT) in group 2 were significantly more than other groups (P < 0.05). Ang II infusion resulted in dose-related percentage change increase in RBF and decrease in RVR. However, these responses in the OVX-estradiol and OVX-hypertensive rats were significantly lower than in the OVX-control group (P < 0.05). For instance, at the dose of 1000 ng/kg/min of Ang II administration, the percentage change of RBF was 45.1 ± 10.4%, 17.9 ± 2.3%, and 16.7 ± 4.7% in the groups of 1 to 3, respectively. Conclusion: Losartan prescription in some conditions such as hypertension or ERT could worsen RBF and RVR responses to Ang II.

The Prevention of Cisplatin-Induced Nephrotoxicity: A General Consensus Statement of a Group of Oncologist-Hematologists, Adult and Pediatric Nephrologists, Radiation Oncologists, Clinical Pathologists, Clinical Pharmacologists, and Renal Physiologists on Cisplatin Therapy in Cancer Patients.

Backgrounds: Most of the cancer patients with solid tumor are subjected to chemotherapy with cisplatin (CP) in clinic. However, the most side effect of CP is nephrotoxicity, which limits the treatment. The aim of study was to develop a general consensus statement for CP therapy in clinic to limit the drug-induced nephrotoxicity. Methods: A total of 30 oncologist-hematologists, adult and pediatric nephrologists, radiation oncologists, clinical pathologist clinical pharmacologist, and renal physiologist participated in a workshop, and in order to reduce the incidence of CP-induced nephrotoxicity, a general consensus was developed. Results: The developed general consensus was focused on some items such as age, sex, female hormone, nonsteroidal anti-inflammatory drugs (NSAID), renin-angiotensin system inhibitor drugs, glomerular filtration rate, hydration methods, contrasts, antioxidants, dextrose, and magnesium. Conclusion: The agreement between participants for CP therapy in clinic was achieved, and this general consensus was announced to be implemented in the hospitals.

Intravenous Administration of Cisplatin with Magnesium Sulfate Supplement May Prevent Kidney Toxicity in Rats: The Role of Gender and Magnesium Sulfate Dose.

BACKGROUND: Cisplatin (CP) is widely used to treat various kinds of malignancies, but to avoid its side effects of nephrotoxicity and hypomagnesemia, magnesium supplementation is a subject of debate. The current study was designed to determine the protective role of intravenous magnesium sulfate (MgSO4) against intravenous administration of CP in male and female rats. METHOD: In this case-control experimental study, 80 Wistar male and female rats in 12 groups of experiments were subjected to receive intravenous administration of CP accompanied with intravenous infusion of different doses (1, 3, and 10 mg/ml solution) of MgSO4 and were compared with the control groups. RESULTS: CP administration increased blood urea nitrogen (BUN), creatinine (Cr), kidney tissue damage score (KTDS), and kidney weight (KW), and they were attenuated by the mid-dose of MgSO4 supplementation in female rats. However, in male rats, the increase of Cr, BUN, KTDS, and KW induced by CP was ameliorated by low, mid-, and high doses of MgSO4 supplements. The levels of these markers were significantly different between male and female rats in the mid-dose of MgSO4-treated group (BUN: P=0.002, Cr: P=0.005, KTDS: P=0.002, and KW: P=0.031). CP reduced clearance of Cr (ClCr) in both male and female rats significantly compared to the control group of saline alone (P male = 0.002 and P female = 0.001), and the mid- and high doses of MgSO4 supplements improved ClCr in female rats. There were also sex differences in ClCr in mid- (P=0.05) and high (P=0.032) doses of MgSO4-treated groups. CP accompanied with the mid-dose of MgSO4 supplement reduced the KTDS (P male = 0.04 and P female = 0.004) and KW (P male = 0.002 and P female = 0.042) in both male and female rats significantly when compared with the CP-alone-treated group, while there were also significant differences between the sexes (KTDS: P=0.002 and KW: P=0.031). CP accompanied with three different doses of MgSO4 supplements did not improve the serum levels of lactate dehydrogenase, urine level of sodium, malondialdehyde, urine flow, and nitrite statistically when compared with the CP-alone-treated group. CONCLUSION: The renal protective effect of MgSO4 could be dose and gender related.

Hydration with Mannitol and Dextrose May Promote Cisplatin-Induced Nephrotoxicity: Test of Five Protocols of Hydration during Cisplatin Therapy in Rat Models.

BACKGROUNDS: Cisplatin (CP) still is a novel choice for solid tumor therapy, but it is accompanied with the side effect of nephrotoxicity. Hydration may reduce the risk of CP-induced nephrotoxicity, while the issue is still challenging. In this study, five types of hydration protocols including saline, mannitol, dextrose saline, saline plus furosemide, and saline plus mannitol were examined in both sexes of rats during CP therapy. METHODS: Seventy-six male and female Wistar rats in 14 groups of experiments were subjected to CP therapy, and five types of hydration protocols were implemented, and the induced nephrotoxicity was evaluated via biochemical markers, kidney function parameters, and pathology investigation. RESULTS: Male and female rats had different responses to hydration protocol types. The higher mortality rate was seen in female rats that received mannitol or dextrose hydration types. In addition, the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and sodium excretion fraction (ENa%) increased and the clearance of Cr (ClCr) decreased significantly (P < 0.05) in female rats hydrated with saline plus furosemide or mannitol plus saline-treated groups. The worsened condition in male rats is observed in the mannitol hydration group with a significant decrease of ClCr and significant increase of serum BUN and Cr and ENa% (P < 0.05). The higher kidney tissue damage score (KTDS) in the mentioned groups verified the findings. CONCLUSION: Hydration with mannitol or dextrose promotes the risk of nephrotoxicity during CP therapy with more intensity on the female.

Protective Role of Angiotensin II Type 1 Receptor Blocker on Short Time Effect of Oleic Acid Induced Lung and Kidney Injury.

BACKGROUNDS: Acute respiratory distress syndrome (ARDS) causes high mortality rate in clinic, and the pathogenesis of this syndrome may interact with renin angiotensin system (RAS) components. The main objective of this study was to determine the protective role of AT1R antagonist (losartan) on oleic acid (OA) induced ARDS and kidney injury. METHODS: The animal model of ARDS was performed by intravenous administration of 250 µl/kg oleic acid (OA). Male and female rats were subjected to received intravenously vehicle (saline, groups 1 and 4), OA (groups 2 and 5), or losartan (10 mg/kg) plus OA (groups 3 and 6), and six hour later, the measurements were performed. RESULTS: Co-treatment of OA and losartan increased the serum levels of blood urea nitrogen significantly (P < 0.05) and creatinine insignificantly in both gender. However, the OA induced kidney damage was decreased by losartan significantly in male (P < 0.05) and insignificantly in female rats. In addition, co-treatment of OA and losartan decreased lung water content significantly in male rats (P < 0.05). Based on tissue staining, no significant difference in lung tissue damages were observed between the groups, however some exudate were observed in lung male rats treated with OA alone which were abolished by losartan. CONCLUSIONS: Losartan may protect the kidney and lung against OA induced tissue injury in male rats. This protective action is not certain in female rats.

Mas Receptor Blockade Promotes Renal Vascular Response to Ang II after Partial Kidney Ischemia/Reperfusion in a Two-Kidney-One-Clip Hypertensive Rats Model.

BACKGROUND: Partial kidney ischemia-reperfusion (IR) injury is the principal cause of acute kidney injury. The renin-angiotensin system (RAS) and hypertension also may be influenced by renal IR injury. In two models of partial renal IR with and without ischemia preconditioning (IPC) and using Mas receptor (MasR) blockade, A779 or its vehicle, the renal vascular responses to angiotensin II (Ang II) administration in two-kidney-one-clip (2K1C) hypertensive rats were determined. METHODS: Thirty-seven 2K1C male Wistar rats with systolic blood pressure ≥150 mmHg were randomly divided into three groups; sham, IR, and IPC + IR. The animals in the sham group underwent surgical procedures except partial IR. The rats in the IR group underwent 45 min partial kidney ischemia, and the animals in the IPC + IR group underwent two 5 min cycles of partial kidney ischemia followed by 10 min reperfusion and partial kidney ischemia for 45 min. The renal vascular responses to graded Ang II (30, 100, 300, and 1000 ng kg-1.min-1) infusion using A779 or its vehicle were measured at constant renal perfusion pressure. RESULTS: Four weeks after 2K1C implementation, the intravenous infusion of graded Ang II resulted in dose-related increases in mean arterial pressure (MAP) (P dose < 0.0001) that was not different significantly between the groups. No significant differences were detected between the groups in renal blood flow (RBF) or renal vascular resistance (RVR) responses to Ang II infusion when MasR was not blocked. However, by MasR blockade, these responses were increased in IR and IPC + IR groups that were significantly different from the sham group (P < 0.05). For example, infusion of Ang II at dose 1000 ng kg-1.min-1 resulted in decreased RBF percentage change (RBF%) from the baseline to 17.5 ± 1.9%, 39.7 ± 3.8%, and 31.0 ± 3.4% in sham, IR, and IPC + IR, respectively. CONCLUSION: These data revealed the important role of MasR after partial kidney IR in the responses of RBF and RVR to Ang II administration in 2K1C hypertensive rats.

Renal Vascular Response to Angiotensin II Administration in Two Kidneys-One Clip Hypertensive Rats Treated with High Dose of Estradiol: The Role of Mas Receptor.

BACKGROUNDS: High blood pressure is one of the most important causes of death around the world. The renin-angiotensin system (RAS) and estradiol are two important items that regulate arterial blood pressure in women. However, hypertension, RAS, and sex hormone estradiol may influence renal vascular responses. This study was designed to determine the role of Mas receptor (MasR) on renal vascular response to angiotensin II (Ang II) administration in two kidneys-one clip (2K1C) hypertensive rats treated with estradiol. METHOD: The ovariectomized rats were subjected to 2K1C or non-2K1C and simultaneously treated with estradiol (500 µg/kg/weekly) or placebo for a period of 4 weeks. Subsequently, under anesthesia, renal vascular responses to graded doses of Ang II administration with MasR blockade (A779) or its vehicle were determined. RESULTS: A779 or its vehicle did not alter mean arterial pressure (MAP), renal perfusion pressure (RPP), and renal blood flow (RBF). However, in non-2K1C rats, Ang II infusion decreased RBF and increased renal vascular resistance (RVR) responses in a dose-related manner (Ptreat < 0.0001). The greatest responses were found in ovariectomized estradiol-treated rats that received A779 (Pgroup < 0.05) in non-2K1C rats. Such findings were not detected in 2K1C hypertensive rats. For example, in estradiol-treated rats that received A779, at 1000 ng/kg/min of Ang II infusion, RBF reduced from 1.6 ± 0.2 to 0.89 ± 0.19 ml/min in non-2K1C rats, and it reduced from 1.6 ± 0.2 to 1.2 ± 0.2 ml/min in 2K1C rats. CONCLUSION: Hypertension induced by 2K1C may attenuate the role of A779 and estradiol in renal vascular responses to Ang II infusion. Perhaps, this response can be explained by the reduction of Ang II type 1 receptor (AT1R) expression in the 2K1C hypertensive rats.

Sex Differences in the Renal Vascular Responses of AT1 and Mas Receptors in Two-Kidney-One-Clip Hypertension.

BACKGROUND: The prevalence and severity of hypertension, as well as the activity of the systemic and local renin angiotensin systems (RASs), are gender related, with more symptoms in males than in females. However, the underlying mechanisms are not well understood. In this study, we investigated sex differences in renal vascular responses to angiotensin II (Ang II) administration with and without Ang II type 1 and Mas receptor (AT1R and MasR) antagonists (losartan and A779) in the 2K1C rat model of renovascular hypertension. METHODS: Male and female 2K1C rats were divided into 8 experimental groups (4 of each sex) treated with vehicle, losartan, A779, or A779+losartan. Responses of mean arterial pressure (MAP), renal blood flow (RBF), and renal vascular resistance (RVR) to Ang II were determined. RESULTS: In both sexes, the basal MAP, RBF, and RVR were not significantly different between the four groups during the control period. The Ang II administration decreased RBF and increased RVR in a dose-related manner in both sexes pretreated with vehicle or A779 (P dose < 0.0001), but in vehicle pretreated groups, RBF and RVR responses were different between male and female rats (P group < 0.05). AT1R blockade increased RBF and decreased RVR responses to Ang II, and no difference between the sexes was detected. Coblockades of AT1R and MasR receptors increased RBF response to Ang II significantly in males alone but not in females (P group=0.04). CONCLUSION: The impact of Ang II on RBF and RVR responses seems to be gender related with a greater effect on males, and this sex difference abolishes by Mas receptor blockade. However, the paradoxical role of dual losartan and A779 may provide the different receptor interaction in RAS between male and female rats.

The Effect of Type of Delivery on the Nitric Oxide Metabolites and Endothelial Dysfunction in Pregnant Women.

BACKGROUND: Since endothelial dysfunction is related to atherosclerosis, this study was planned to determine the effect of type of delivery on Nitric Oxide (NO) metabolites and endothelial function. MATERIALS AND METHODS: This Cohort study was conducted in 2015 in selected hospitals of Isfahan. 88 nulliparous women with gestational age of 39 weeks and above were enrolled in this study using convenience sampling method and finally, after giving birth, 51 mothers with vaginal delivery, 21 with urgent C-section and 13 with elective C-section were considered for data analysis. The serum levels of NO metabolites were measured in the laboratory with standard kits and data was analyzed using student and paired t-test, one-way ANOVA, and Chi-square test. The significance level was considered less than 0.05 for all tests. RESULTS: The NO metabolites levels in mothers who had vaginal delivery or urgent C-section showed a significant difference before and after delivery (normal vaginal delivery (NVD): t50 = 5.61, p < 0.001, Urgent C-section: t23 = 5.38, p < 0.001). But those with elective C-section showed no significant difference in the nitrate and total nitrite levels before and after delivery (p > 0.05). CONCLUSIONS: Since reduction in serum levels of NO metabolites may possibly indicate endothelial dysfunction and predict cardiovascular disease, especially atherosclerosis in the future, it could be concluded that, childbirth, regardless of the type of delivery, could damage the endothelial cells but C-section (urgent or elective) could cause more disruption than vaginal delivery.