Preventive effects of nitric oxide donors in contrast-induced nephropathy in patients undergoing coronary artery angiography: an updated systematic review and meta-analysis of 13 randomized controlled trials.

Background: Contrast-induced nephropathy (CIN) is associated with increased mortality and morbidity in patients undergoing coronary angiography (CAG) and percutaneous coronary intervention (PCI). We aimed to assess the latest evidence on the preventive effects of nitric oxide (NO) donors in CIN in patients undergoing CAG/PCI. Methods: We conducted a systematic review and meta-analysis of RCTs from PubMed, Web of Science, Scopus, Embase, and Cochrane searches until May 5th, 2024. Dichotomous data were pooled using risk ratio (RR), and continuous data were pooled using mean difference (MD), both with a 95% confidence interval (CI), using (R version 4.3). Results: Our analysis included 13 RCTs encompassing 3,550 patients. NO donors were significantly associated with a decreased incidence of CIN compared to placebo either as an oral administration (RR: 0.33 with 95% CI [0.26, 0.42], P< 0.01) or IV infusions (RR: 0.56 with 95% CI [0.40, 0.78], P< 0.01). Moreover, NO donors were significantly associated with decreased serum creatinine levels compared to placebo either as an oral administration (MD: -0.07 with 95% CI [-0.10, -0.04], P< 0.01) or IV infusions (MD: -0.07 with 95% CI [-0.09, -0.04], P< 0.01). In terms of safety, NO donors were significantly associated with a decreased incidence of MACE compared to placebo as an oral administration (RR: 0.64 with 95% CI [0.45, 0.89], P< 0.01). However, there was no significant difference between NO donors as IV infusions and placebo in MACE (RR: 0.68 with 95% CI [0.38, 1.21], P= 0.18). Finally, NO donors were significantly associated with a decreased incidence of all-cause mortality compared to placebo as an oral administration (RR: 0.58 with 95% CI [0.36, 0.94], P= 0.03). However, there was no significant difference between NO donors as IV infusions and placebo in all-cause mortality (RR: 1.84 with 95% CI [0.40, 8.52], P= 0.44). Conclusion: NO donors as an adjunct therapy are associated with reduced incidence of CIN, and decreased serum creatinine levels either as an oral or IV administration. Also, it was associated with decreased incidence of MACE and all-cause mortality as an oral administration which make this simple low-cost intervention an important therapeutic option in patients undergoing CAG/PCI.

Cervical priming before first-trimester surgical abortion is recommended in certain groups of women. Nitric oxide (NO) donors induce cervical ripening without uterine contractions, but the efficacy and side effects are of concern. To evaluate NO donors for cervical ripening before first-trimester surgical abortion, in terms of efficacy, side effects, and reduction of complications. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and POPLINE. We also searched reference lists of retrieved papers. We contacted experts in the field for information on both published and unpublished trials. Randomised controlled trials comparing NO donors alone or in combination with other methods for cervical ripening in first-trimester surgical abortion. Two review authors independently selected and extracted the data onto a data extraction form. We processed the data using Review Manager (RevMan 5) software. We included 9 studies involving 766 participants. There were no serious complications (infection requiring antibiotic treatment, blood transfusion, complications requiring unintended operation, cervical injury, uterine perforation, death or serious morbidity) in the included trials.NO donors were more effective in cervical ripening when compared with placebo or no treatment. Baseline cervical dilatation before the procedure was higher in NO donors group (mean difference (MD) 0.30, 95% confidence interval (CI) 0.01 to 0.58) The cumulative force required to dilate the cervix to 8 mm (MD -4.29, 95% CI -9.92 to 1.35), headache (risk ratio (RR) 1.73, 95% CI 0.86 to 3.46), abdominal pain (RR 0.87, 95% CI 0.50 to 1.50), or patient satisfaction (RR 0.95, 95% CI 0.84 to 1.07) were not different. More nausea and vomiting occurred in the women who received a NO donor (RR 2.62, 95% CI 1.07 to 6.45).NO donors were inferior to prostaglandins for cervical ripening. The cumulative force required to dilate the cervix to 8 mm to 9 mm was higher (MD 13.12, 95% CI 9.72 to 16.52), and baseline cervical dilatation was less (MD -0.73, 95% CI -1.01 to -0.45) in the NO donor group. However, the probability of dilation greater than 8 mm at three hours was higher in the NO donor group (RR 6.67, 95% CI 2.21 to 20.09). Side effects including headache (RR 5.13, 95% CI 3.29 to 8.00), palpitation (RR 3.43, 95% CI 1.64 to 7.15), dizziness (RR 3.29, 95% CI 1.46 to 7.41), and intraoperative blood loss (MD 33.59 ml, 95% CI 24.50 to 42.67) were also higher. However, abdominal pain (RR 0.33, 95% CI 0.25 to 0.44) and vaginal bleeding (RR 0.14, 95% CI 0.07 to 0.27) were less in the NO donor group. No difference for nausea/vomiting in both groups(RR 1.17, 95% CI 0.94 to 1.46). Patient satisfaction was not different.One trial compared a NO donor with a NO donor plus prostaglandin. The cumulative force required to dilate the cervix to 8 mm was higher (MD 14.50, 95% CI 0.50 to 28.50) in the NO donor group. There was no difference in headache (RR 0.88, 95% CI 0.38 to 2.00), abdominal pain (RR 0.14, 95% CI 0.02 to 1.07), or intraoperative blood loss (MD -50, 95% CI -164.19 to 64.19). NO donors are superior to placebo or no treatment, but inferior to prostaglandins for first-trimester cervical ripening, and associated with more side effects.

Effects of nitric oxide donors on basal and K +-evoked release of [formula omitted]noradrenaline from rat cerebral cortex synaptosomes

Effect of nitric oxide donors on extracellular ATP, ADP, and AMP catabolism in rat hippocampal synaptosomes

PurposeTo evaluate the effect of nitric oxide (NO) donor, in combination with plasma volume expansion, on both fetal and maternal outcomes in pregnancies complicated by early-onset fetal growth restriction (FGR).MethodsA total of 40 pregnant women diagnosed with early onset FGR were recruited from Ain Shams University Maternity Hospital between June 2023 to December 2023. The patients were randomly assigned into two groups, 20 in each group. Group A received Nitroderm TTS ® 5 mg for 12 h daily with plasma volume expansion (PVE) in the form of 2.5 L of water per day. Group B represented the control group. The primary endpoint of the study, assessed after 2 weeks of treatment initiation, focused on fetal growth parameters as the primary outcome. In addition, amniotic fluid volume, umbilical artery Doppler changes, development of fetal complications, maternal vital signs, and any side effects, were recorded. At the time of delivery, the following also documented: timing, mode, and interval to delivery, along with neonatal outcomes.ResultsGroup A exhibit statistically significant enhancement in fetal growth compared to Group B in terms of estimated fetal weight, abdominal circumference, head circumference, biparietal diameter, femur length, amniotic fluid volume, and umbilical artery pulsatility index. Furthermore, Group A demonstrated more favorable outcomes in terms of gestational age at delivery, interval to delivery, birth weight, APGAR score and rates of NICU admission.ConclusionThe combination of NO donors and PVE has shown promising results in enhancing fetal growth and extending gestation. This study adds to the existing body of evidence supporting the effectiveness of NO donor therapy when used in conjunction with fluid management for managing FGR. Nonetheless, additional research is essential to validate these results and refine the treatment strategy for optimal outcomes in affected pregnancies.

Effects of nitric oxide donors on the afferent resting activity in the cephalopod statocyst

Effect of nitric oxide donors on NADPH oxidase signaling pathway in human neutrophils in vitro

Cervical priming before first-trimester surgical abortion is recommended in certain groups of women. Nitric oxide (NO) donors induce cervical ripening without uterine contractions, but the efficacy and side effects are of concern. To evaluate efficacy, side effects and complications of NO donors for cervical ripening before first-trimester surgical abortion. We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE and Popline. We also searched reference lists of retrieved papers. We contacted experts in the field for information on both published and unpublished trials. Randomised controlled trials comparing NO donors alone or in combination with other methods for cervical ripening in first-trimester surgical abortion. Two reviewers independently selected and extracted the data onto a data extraction form. We processed the data using Review Manager (RevMan5) software. We included eight studies involving 718 participants. There were no serious complications (infection requiring antibiotic treatment, blood transfusion, complications requiring unintended operation, cervical injury, uterine perforation, death or serious morbidity) in the trials included.NO donors were ineffective in cervical ripening comparing with placebo or no treatment. The cumulative force required to dilate the cervix to 8 mm (mean difference -4.29, 95% CI -9.92, 1.35), baseline cervical dilatation before the procedure (mean difference 0.21, 95% CI -0.12, 0.53), headache (RR 1.73, 95% CI 0.86, 3.46), abdominal pain (RR 0.87, 95% CI 0.51, 1.50) or patient satisfaction (RR 0.95, 95% CI 0.84, 1.07) were not different. More nausea and vomiting occurred in the women who received a NO donor (RR 2.62, 95% CI 1.07, 6.75).NO donors were inferior to prostaglandins for cervical ripening. The cumulative force required to dilate the cervix to 8-9 mm was higher (mean difference 13.12, 95% CI 9.72, 16.52) and baseline cervical dilatation was less (mean difference -0.73, 95% CI -1.01, -0. 45) in the NO donor group. Side effects including headache (RR 5.13, 95% CI 3.29, 8.00), palpitation (RR 3.43, 95% CI 1.64, 7.15), dizziness (RR 3.29, 95% CI 1.46, 7.41) and intraoperative blood loss (mean difference 33.59 ml, 95% CI 24.50, 42.67) were also higher. However, abdominal pain (RR 0.33, 95% CI 0.25, 0.44) and vaginal bleeding (RR 0.14, 95% CI 0.07, 0.27) was less in the NO donor group. Patient satisfaction was not different.One trial compared a NO donor with a NO donor plus prostaglandin. The cumulative force required to dilate the cervix to 8 mm was higher (mean difference 14.50, 95% CI 0.50, 28.50) in the NO donor group. There was no difference in headache (RR 0.88, 95% CI 0.38, 2.00), abdominal pain (RR 0.14, 95% CI 0.02, 1.07) or intraoperative blood loss (mean difference -50, 95% CI -164.19, 64.19). NO donors are inferior to prostaglandins for first-trimester cervical ripening, and associated with more side effects. NO donors are comparable to placebo and no treatment for cervical ripening.

Cervical priming before first-trimester surgical abortion is recommended in certain groups of women. Nitric oxide (NO) donors induce cervical ripening without uterine contractions, but the efficacy and side effects are of concern. To evaluate efficacy, side effects and complications of NO donors for cervical ripening before first-trimester surgical abortion. We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE and POPLINE. We also searched reference lists of retrieved papers. We contacted experts in the field for information on both published and unpublished trials. Randomised controlled trials comparing NO donors alone or in combination with other methods for cervical ripening in first-trimester surgical abortion. Two reviewers independently selected and extracted the data onto a data extraction form. We processed the data using Review Manager (RevMan5) software. We included nine studies involving 766 participants. There were no serious complications (infection requiring antibiotic treatment, blood transfusion, complications requiring unintended operation, cervical injury, uterine perforation, death or serious morbidity) in the trials included.NO donors were more effective in cervical ripening comparing with placebo or no treatment. Baseline cervical dilatation before the procedure was higher in NO donors group (mean difference 0.30, 95% CI 0.01, 0.58) The cumulative force required to dilate the cervix to 8 mm (mean difference -4.29, 95% CI -9.92, 1.35), headache (RR 1.73, 95% CI 0.86, 3.46), abdominal pain (RR 0.87, 95% CI 0.50, 1.50) or patient satisfaction (RR 0.95, 95% CI 0.84, 1.07) were not different. More nausea and vomiting occurred in the women who received a NO donor (RR 2.62, 95% CI 1.07, 6.45).NO donors were inferior to prostaglandins for cervical ripening. The cumulative force required to dilate the cervix to 8-9 mm was higher (mean difference 13.12, 95% CI 9.72, 16.52) and baseline cervical dilatation was less (mean difference -0.73, 95% CI -1.01, -0.45) in the NO donor group. Side effects including headache (RR 5.13, 95% CI 3.29, 8.00), palpitation (RR 3.43, 95% CI 1.64, 7.15), dizziness (RR 3.29, 95% CI 1.46, 7.41) and intraoperative blood loss (mean difference 33.59 ml, 95% CI 24.50, 42.67) were also higher. However, abdominal pain (RR 0.33, 95% CI 0.25, 0.44) and vaginal bleeding (RR 0.14, 95% CI 0.07, 0.27) was less in the NO donor group. Patient satisfaction was not different.One trial compared a NO donor with a NO donor plus prostaglandin.The cumulative force required to dilate the cervix to 8 mm was higher (mean difference 14.50, 95% CI 0.50, 28.50) in the NO donor group. There was no difference in headache (RR 0.88, 95% CI 0.38, 2.00), abdominal pain (RR 0.14, 95% CI 0.02, 1.07) or intraoperative blood loss (mean difference -50, 95% CI -164.19, 64.19). NO donors are superior to placebo or no treatment, but inferior to prostaglandins for first-trimester cervical ripening, and associated with more side effects.

The effect of nitric oxide (NO) donors on survival of conidia, germination and growth of the opportunistic pathogenic fungus Aspergillus fumigatus was investigated. Most efficient was sodium nitrite in an acidic milieu (pH 4.5). At a concentration of 5 mmol/L it killed all resting conidia in buffer within 16 h. S-Nitroso derivatives of thiols (cysteine, N-acetylcysteine and N-acetylpenicillamine) at the same concentration killed about 30-50% of spores within 24 h. The NO scavenger, oxyhemoglobin, abolished these effects. S-Nitrosoglutathione had no fungicidal effect and promoted germination. Sodium nitrite and S-nitroso-N-acetylcysteine inhibited germination of conidia in various media from concentration of 0.5 mmol/L and stopped it at concentrations of 1.4-2.9 mmol/L. In media with glucose and casein hydrolyzate or sodium nitrate as nitrogen source, growth inhibition by sodium nitrite (0.5-2 mmol/L) was only weak and mostly transient. In general, the used strain A. fumigatus seems to be less sensitive to nitric oxide donors than dimorphic pathogenic fungi. Thus, nitric oxide is probably not a major effector molecule in killing phagocytized elements of this fungus by host's immunocytes.

It is unclear whether blood pressure should be altered actively during the acute phase of stroke. This is an update of a Cochrane review first published in 1997, and previously updated in 2001 and 2008. To assess the clinical effectiveness of altering blood pressure in people with acute stroke, and the effect of different vasoactive drugs on blood pressure in acute stroke. We searched the Cochrane Stroke Group Trials Register (last searched in February 2014), the Cochrane Database of Systematic reviews (CDSR) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 2), MEDLINE (Ovid) (1966 to May 2014), EMBASE (Ovid) (1974 to May 2014), Science Citation Index (ISI, Web of Science, 1981 to May 2014) and the Stroke Trials Registry (searched May 2014). Randomised controlled trials of interventions that aimed to alter blood pressure compared with control in participants within one week of acute ischaemic or haemorrhagic stroke. Two review authors independently applied the inclusion criteria, assessed trial quality and extracted data. The review authors cross-checked data and resolved discrepancies by discussion to reach consensus. We obtained published and unpublished data where available. We included 26 trials involving 17,011 participants (8497 participants were assigned active therapy and 8514 participants received placebo/control). Not all trials contributed to each outcome. Most data came from trials that had a wide time window for recruitment; four trials gave treatment within six hours and one trial within eight hours. The trials tested alpha-2 adrenergic agonists (A2AA), angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor antagonists (ARA), calcium channel blockers (CCBs), nitric oxide (NO) donors, thiazide-like diuretics, and target-driven blood pressure lowering. One trial tested phenylephrine.At 24 hours after randomisation oral ACEIs reduced systolic blood pressure (SBP, mean difference (MD) -8 mmHg, 95% confidence interval (CI) -17 to 1) and diastolic blood pressure (DBP, MD -3 mmHg, 95% CI -9 to 2), sublingual ACEIs reduced SBP (MD -12.00 mm Hg, 95% CI -26 to 2) and DBP (MD -2, 95%CI -10 to 6), oral ARA reduced SBP (MD -1 mm Hg, 95% CI -3 to 2) and DBP (MD -1 mm Hg, 95% CI -3 to 1), oral beta blockers reduced SBP (MD -14 mm Hg; 95% CI -27 to -1) and DBP (MD -1 mm Hg, 95% CI -9 to 7), intravenous (iv) beta blockers reduced SBP (MD -5 mm Hg, 95% CI -18 to 8) and DBP (-5 mm Hg, 95% CI -13 to 3), oral CCBs reduced SBP (MD -13 mmHg, 95% CI -43 to 17) and DBP (MD -6 mmHg, 95% CI -14 to 2), iv CCBs reduced SBP (MD -32 mmHg, 95% CI -65 to 1) and DBP (MD -13, 95% CI -31 to 6), NO donors reduced SBP (MD -12 mmHg, 95% CI -19 to -5) and DBP (MD -3, 95% CI -4 to -2) while phenylephrine, non-significantly increased SBP (MD 21 mmHg, 95% CI -13 to 55) and DBP (MD 1 mmHg, 95% CI -15 to 16).Blood pressure lowering did not reduce death or dependency either by drug class (OR 0.98, 95% CI 0.92 to 1.05), stroke type (OR 0.98, 95% CI 0.92 to 1.05) or time to treatment (OR 0.98, 95% CI 0.92 to 1.05). Treatment within six hours of stroke appeared effective in reducing death or dependency (OR 0.86, 95% CI 0.76 to 0.99) but not death (OR 0.70, 95% CI 0.38 to 1.26) at the end of the trial. Although death or dependency did not differ between people who continued pre-stroke antihypertensive treatment versus those who stopped it temporarily (worse outcome with continuing treatment, OR 1.06, 95% CI 0.91 to 1.24), disability scores at the end of the trial were worse in participants randomised to continue treatment (Barthel Index, MD -3.2, 95% CI -5.8, -0.6). There is insufficient evidence that lowering blood pressure during the acute phase of stroke improves functional outcome. It is reasonable to withhold blood pressure-lowering drugs until patients are medically and neurologically stable, and have suitable oral or enteral access, after which drugs can than be reintroduced. In people with acute stroke, CCBs, ACEI, ARA, beta blockers and NO donors each lower blood pressure while phenylephrine probably increases blood pressure. Further trials are needed to identify which people are most likely to benefit from early treatment, in particular whether treatment started very early is beneficial.

Effects of nitric oxide donors on vascular endothelial growth factor gene induction

Objective: To investigate the incidence and risk factors of contrast-induced nephropathy (CIN) in patients receiving coronary angiography (CAG) in a Chinese medical center. Methods: The medical records of the patients receiving CAG at Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiaotong University from January 2008 to July 2009 were collected to analyze the incidence of CIN under different conditions and the clinical difference between CIN group and non-CIN group. Results: There were 487 cases enrolled in this study and the total incidence of CIN was 10.5%. Through Mehran risk score stratification, incidence of CIN increased with risk scores and in an extremely high-risk group it was as high as 18.0%. Multi-factor regression analysis showed that preoperative hypotension, heart failure, anemia and low estimated glomerular filtration rate (≤30 mL/min) were risk factors of CIN after CAG. Conclusion: CIN post CAG is associated with preoperative hypotension, heart failure, anemia and renal function. Close attention should be paid to CIN in patients receiving CAG.

Effect of Nitric Oxide Donors on Blood Pressure and Pulse Pressure in Acute and Subacute Stroke

The abilities of such therapeutic nitrovasodilators as sodium nitroprusside (SNP) and glyceryl trinitrate (GTN) to dilate vascular smooth muscles (VSM) and affect intracellular calcium concentration level ([Ca2+]i) in a rat tail artery were tested under different types of preactivation. To shed light on mechanisms underlying possible differences in the action of these two nitric oxide (NO) donors, simultaneous measurements of [Ca2+]i and contractile force were done. All vascular rings were precontracted either using a high-K+-Krebs solution or phenylephrine (PE). It was shown that the effect of both NO donors strongly depended on a type of VSM preactivation. The EC50 for GTN under K+ stimulation of VSM comprised (2.48 +/- 1.6) x 10(-5) M, whereas the mean EC50 under PE stimulation was (3.05 +/- 2.3) x 10(-4) M (p < 0.05, n = 9). The EC50 for SNP under K+ stimulation of VSM comprised (1.09 +/- 0.47) x 10(-7) M, whereas the EC(50) under PE stimulation was (8.01 +/- 2.4) x 10(-6) M (p < 0.05, n = 9). GTN demonstrated a significant discrepancy in the magnitude of changes in [Ca2+]i and related VSM relaxant responses, indicating the ability of GTN to relax VSM in the absence of a proportional decrease in [Ca2+]i. The main peculiarity of SNP action under K+ stimulation as compared to PE stimulation was the transient decrease in [Ca2+]i while relaxation was sustained. Therefore, both NO donors demonstrated their ability to produce vasorelaxation as a result of an alteration in myofilament calcium sensitivity. These data clearly indicate that the sensitivity of VSM to NO donors is higher under K+ depolarization than that seen under PE stimulation, indicating that Ca2+ entry through voltage-operated calcium channels is more sensitive to NO as compared to calcium mobilization by means of Ca2+ entry through receptor- operated calcium channels or intracellular Ca2+ release, or both.