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Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...
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Vasodilators, primarily affecting the smooth muscles within arterial and venous walls, are commonly used for hypertension treatment. Medications such as minoxidil and hydralazine primarily target arteries and arterioles, while sodium nitroprusside acts on arterioles and venules. Minoxidil, functioning as a prodrug, is metabolized by hepatic sulfotransferase into its active form, minoxidil sulfate, after oral administration. This metabolite binds to the sulfonylurea receptor (SUR) component of...

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Swimming Exercise Protocol and Care Methods for Pregnant Rats
05:17

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Published on: April 5, 2024

A profound decrease in maternal arginine uptake provokes endothelial nitration in the pregnant rat.

Ran Reshef1, Doron Schwartz, Merav Ingbir

  • 1Department of Nephrology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel.

American Journal of Physiology. Heart and Circulatory Physiology
|December 25, 2007
PubMed
Summary
This summary is machine-generated.

Maternal arginine uptake decreases during pregnancy, impacting endothelial function. This reduction is linked to increased protein nitration and may contribute to endothelial dysfunction, such as preeclampsia.

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Published on: January 26, 2024

Area of Science:

  • Physiology
  • Biochemistry
  • Reproductive Biology

Background:

  • Nitric oxide (NO) generation increases during pregnancy, with L-arginine as its precursor.
  • Cationic amino acid transporter-1 (CAT-1) is crucial for endothelial NO synthase (eNOS) arginine transport.
  • Pregnancy increases fetal demand for arginine, potentially altering maternal arginine uptake.

Purpose of the Study:

  • To investigate compensatory changes in maternal arginine uptake by the endothelium during pregnancy.
  • To test the hypothesis that altered maternal arginine uptake affects endothelial function in pregnant rats.

Main Methods:

  • Measurement of radiolabeled L-[3H]arginine uptake in maternal aortic rings from pregnant and virgin rats.
  • Assessment of endothelial protein nitration using Western blotting and immunohistochemistry.
  • Analysis of aortic CAT-1 mRNA and protein levels via Northern blot and Western blotting.
  • Evaluation of protein kinase C (PKC)-alpha expression and CAT-1 phosphorylation.
  • Administration of alpha-tocopherol (PKC-alpha inhibitor) to assess its effects on arginine transport and protein nitration.

Main Results:

  • Arginine uptake in aortic rings decreased significantly in mid- and late-pregnant rats compared to virgin controls.
  • Endothelial protein nitration, indicating peroxynitrite generation and damage, significantly increased during pregnancy.
  • CAT-1 mRNA levels remained unchanged, but CAT-1 protein abundance increased, peaking at mid-pregnancy.
  • PKC-alpha protein content and CAT-1 phosphorylation increased in pregnant rats.
  • Alpha-tocopherol administration prevented the reduction in arginine transport and attenuated protein nitration.

Conclusions:

  • Maternal aortic arginine uptake is reduced during pregnancy, mediated by posttranslational modification of CAT-1 protein, likely via PKC-alpha upregulation.
  • This impaired arginine transport is associated with increased endothelial protein nitration.
  • These findings suggest a potential mechanism contributing to endothelial dysfunction in conditions like preeclampsia.