L-arginine supplementation lowers blood pressure, protein excretion and plasma lipid profile in experimental salt-induced hypertension in pregnancy: Relevance to preeclampsia

Arikawe, AP; Udenze, Ifeoma; Olusanya, Adedunni; Akinnibosun, Olutope Arinola; Dike, I.; Duru, B.N.

doi:10.1016/j.pathophys.2019.02.002

Cited by 11 publications

(11 citation statements)

References 66 publications

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“…e weight of the foetal rat on the 19th day of gestation varied slightly in different reports. In our study, the foetal weights in normal salt intake groups are comparable to that reported by Arikawe et al [18]. However, foetal weight was obviously lower in the hypertensive pregnant rats than the control pregnant rats, and RES supplementation partly reversed this trend (all P < 0.05).…”

Section: Discussionsupporting

confidence: 90%

“…Forty female rats were randomized into four groups (10 rats/group)s: Normal Preg: the rats were fed with normal salt chow (0.9% NaCl) for 10 weeks; Normal Preg + RES: rats were fed with the same feeding regimens as the Normal Preg group, plus daily oral RES (250 mg/kg/day, by intragastric gavage) for 4 weeks (from the 7th week till the 10th week); Salt Preg: the rats were fed with high-salt chow (8% NaCl) [18] for 10 weeks; Salt Preg + RES: rats were fed with the same feeding regimens as the Salt Preg group, plus daily oral RES (250 mg/kg/day, by intragastric gavage) for 4 weeks (from the 7 th week till the 10 th week). We choose high salt intake to induce the PIH model due to its noninvasiveness.…”

Section: Experimental Designmentioning

confidence: 99%

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Resveratrol Supplementation Prevents Hypertension in Hypertensive Pregnant Rats by Increasing Sodium Excretion and Serum Nitric Oxide Level

Jia

Zhang

Guo

et al. 2020

International Journal of Hypertension

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Background. Pregnancy-induced hypertension (PIH) remains a major cause of morbidity and mortality in pregnancy worldwide. This study was designed to study the blood pressure-lowering effect of resveratrol (RES) in a salt-induced hypertensive pregnant rat model. Methods. Forty female Sprague Dawley (SD) rats were randomized into 4 groups: Normal Preg (0.9% salt diet), Normal Preg + RES (0.9% salt diet plus daily oral RES for 4 weeks), Salt Preg (8% salt diet), and Salt Preg + RES (8% salt diet plus daily oral RES for 4 weeks). Noninvasive blood pressure was recorded on gestational days 7 and 14. On the gestational day 19, foetuses were weighed, and blood and urine samples were harvested for electrolytes and biochemical assays. Results. RES significantly reduced SBP, DBP, and MAP on gestational days 7 and 14 in the Salt Preg + RES group compared to the Salt Preg group (all P<0.05). Compared to the Salt Preg group, the foetal weight, serum NO level, urinary sodium, and 24 hour urine volume were significantly increased in the Salt Preg + RES group (all P<0.05). On the contrary, the levels of serum urea, serum creatinine, and urinary protein were significantly decreased in the Salt Preg + RES group compared to the Salt Preg group (all P<0.05). Conclusions. RES decreases blood pressure in a hypertensive pregnant rat model. Increasing sodium excretion and serum nitric oxide level might be, at least part of, the underlying mechanisms.

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Section: Discussionsupporting

confidence: 90%

Section: Experimental Designmentioning

confidence: 99%

Resveratrol Supplementation Prevents Hypertension in Hypertensive Pregnant Rats by Increasing Sodium Excretion and Serum Nitric Oxide Level

Jia

Zhang

Guo

et al. 2020

International Journal of Hypertension

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“…Nonetheless, meta-analyses including these and additional studies concluded that L-arginine is superior to placebo in lowering blood pressure and prolonging pregnancy in women with established PE as well as in reducing the incidence of PE in high-risk women [ 157 , 158 ]. Studies in experimental animals also support the human data showing that treatment with L-arginine ameliorates hypertension during pregnancy [ 109 , 159 , 160 , 161 ]. For instance, 2% L-arginine added to the drinking water of RUPP rats or sFlt-1-infused pregnant rats significantly decreased their blood pressure levels, likely by increasing NO bioavailability and downregulating renal endothelin-1 expression [ 109 , 159 ].…”

Section: Potential Treatment Strategies Targeting To Increase No Bioavailability In Pesupporting

confidence: 56%

Placental Ischemia Says “NO” to Proper NOS-Mediated Control of Vascular Tone and Blood Pressure in Preeclampsia

Palei

Granger

Spradley

2021

IJMS

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In this review, we first provide a brief overview of the nitric oxide synthase (NOS) isoforms and biochemistry. This is followed by describing what is known about NOS-mediated blood pressure control during normal pregnancy. Circulating nitric oxide (NO) bioavailability has been assessed by measuring its metabolites, nitrite (NO2) and/or nitrate (NO3), and shown to rise throughout normal pregnancy in humans and rats and decline postpartum. In contrast, placental malperfusion/ischemia leads to systemic reductions in NO bioavailability leading to maternal endothelial and vascular dysfunction with subsequent development of hypertension in PE. We end this article by describing emergent risk factors for placental malperfusion and ischemic disease and discussing strategies to target the NOS system therapeutically to increase NO bioavailability in preeclamptic patients. Throughout this discussion, we highlight the critical importance that experimental animal studies have played in our current understanding of NOS biology in normal pregnancy and their use in finding novel ways to preserve this signaling pathway to prevent the development, treat symptoms, or reduce the severity of PE.

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“…A small prevention trial reached a similar conclusion, 94 and there is preclinical support that L-arginine could prevent preeclampsia. 95,96 These leads make Larginine a promising concept. It is therefore disappointing that no large clinical trial appears to be registered.…”

Section: Drugs Targeting the Nitric Oxide Synthase Pathwaymentioning

confidence: 99%

Pravastatin, proton-pump inhibitors, metformin, micronutrients, and biologics: new horizons for the prevention or treatment of preeclampsia

Tong

Kaitu’u-Lino

Hastie

et al. 2022

American Journal of Obstetrics and Gynecology

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There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying disease pathophysiology. Molecular targets of candidate treatments include oxidative stress, antiangiogenic factors, and the angiotensin, nitric oxide, and proinflammatory pathways. The proposed treatments undergoing preclinical and clinical trial evaluation are thought to act on placental or endothelial disease or both. Most have adopted the pragmatic strategy of repurposing drugs. Of all the therapeutic agents proposed, pravastatin has received the most interest. There are preclinical studies showing that it has pleiotropic actions that favorably impact on multiple molecular targets and can resolve a preeclampsia phenotype in many animal models. An early phase clinical trial suggests that it may have therapeutic activity. Several large prevention trials are planned or ongoing and, when completed, could definitively address whether pravastatin can prevent preeclampsia. Proton-pump inhibitors, metformin, and sulfasalazine are other drugs with preclinical evidence of multiple molecular actions that could resolve the pathophysiology of preeclampsia. These agents are also currently being evaluated in clinical trials. There have been many recent preclinical studies identifying the potential of numerous natural compounds to treat preeclampsia, such as plant extracts and micronutrients that have potent anti-inflammatory or antioxidant activity. Recent preclinical studies have also proposed novel molecular-targeted strategies, such as monoclonal antibodies targeting tumor necrosis factor alpha, placental growth factor, and short interfering RNA technology, to silence the gene expression of soluble fmslike tyrosine kinase-1 or angiotensinogen. Other treatment approaches that have transitioned to human trials (ranging from single-arm to phase III trials that have been completed or are ongoing) include folic acid, nitric oxide donors (such as L-arginine), recombinant antithrombin III, digoxin immune antigen-binding fragment, and melatonin. There have been case series showing the removal of circulating soluble fms-like tyrosine kinase-1 may help stabilize the disease and prolong pregnancy. Interestingly, there are case reports suggesting that monoclonal antibody eculizumab (complement inhibitor) may have therapeutic potential. If new agents are discovered that are proven to be effective in preventing or treating preeclampsia, the potential to improve global maternal and perinatal health will be significant.

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L-arginine supplementation lowers blood pressure, protein excretion and plasma lipid profile in experimental salt-induced hypertension in pregnancy: Relevance to preeclampsia

Cited by 11 publications

References 66 publications

Resveratrol Supplementation Prevents Hypertension in Hypertensive Pregnant Rats by Increasing Sodium Excretion and Serum Nitric Oxide Level

Resveratrol Supplementation Prevents Hypertension in Hypertensive Pregnant Rats by Increasing Sodium Excretion and Serum Nitric Oxide Level

Placental Ischemia Says “NO” to Proper NOS-Mediated Control of Vascular Tone and Blood Pressure in Preeclampsia

Pravastatin, proton-pump inhibitors, metformin, micronutrients, and biologics: new horizons for the prevention or treatment of preeclampsia

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