Effects of Arginase Inhibition in Hypertensive Hyperthyroid Rats.

Abstract

BACKGROUND:

This study analyzed the effects of chronic administration of N[omega]-hydroxy-nor-l-arginine (nor-NOHA), an inhibitor of arginase, on the hemodynamic, oxidative stress, morphologic, metabolic, and renal manifestations of hyperthyroidism in rats.

METHODS:

Four groups of male Wistar rats were used: control, nor-NOHA-treated (10 mg/kg/day), thyroxine (T4)-treated (75 μg/rat/day), and thyroxine- plus nor-NOHA-treated rats. All treatments were maintained for 4 weeks. Body weight, tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, morphologic, metabolic, plasma, and renal variables were measured. Arginase I and II protein abundance and arginase activity were measured in aorta, heart, and kidney.

RESULTS:

The T4 group showed increased arginase I and II protein abundance, arginase activity, SBP, HR, plasma nitrates/nitrites (NOx), brainstem and urinary isoprostanes, proteinuria and cardiac and renal hypertrophy in comparison to control rats. In hyperthyroid rats, chronic nor-NOHA prevented the increase in SBP and HR and decreased proteinuria in association with an increase in plasma NOx and a decrease in brainstem and urinary isoprostanes. In normal rats, nor-NOHA treatment did not significantly change any hemodynamic, morphologic, or renal variables. Acute nor-NOHA administration did not affect renal or systemic hemodynamic variables in normal or T4-treated rats.

CONCLUSION:

Hyperthyroidism in rats is associated with the increased expression and activity of arginase in aorta, heart, and kidney. Chronic arginase inhibition with nor-NOHA suppresses the characteristic hemodynamic manifestations of hyperthyroidism in association with a reduced oxidative stress. These results indicate an important role for arginase pathway alterations in the cardiovascular and renal abnormalities of hyperthyroidism.

• Authors: Isabel Rodríguez-Gómez, Juan Manuel Moreno, Rosario Jimenez, Andrés Quesada, Sebastian Montoro-Molina, Pablo Vargas-Tendero, Rosemary Wangensteen, Félix Vargas
• Journal: American journal of hypertension (Am J Hypertens) Vol. 28 Issue 12 Pg. 1464-72 (Dec 2015) ISSN: 1941-7225 [Electronic] United States
• PMID: 25907224 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Isoprostanes
• N(omega)-hydroxynorarginine
• Thyroid Hormones
• Nitric Oxide
• Arginine
• Arginase

Topics

• Animals
• Arginase (antagonists & inhibitors, metabolism)
• Arginine (analogs & derivatives, pharmacology, therapeutic use)
• Blood Pressure
• Brain Stem (metabolism)
• Drug Evaluation, Preclinical
• Heart Rate
• Hypertension (drug therapy, etiology, metabolism)
• Hyperthyroidism (complications, drug therapy, metabolism)
• Isoprostanes (urine)
• Male
• Nitric Oxide (blood)
• Random Allocation
• Rats, Wistar
• Renal Circulation (drug effects)
• Thyroid Hormones (blood)