Vasodilator treatment with hydralazine increases blood flow in mdx mice resistance arteries without vascular wall remodelling or endothelium function improvement.

Abstract

BACKGROUND:

Whereas dystrophin has a key role in striated muscle mechanotransduction, its role in vascular functions is not fully understood. In mice lacking dystrophin (mdx) both flow (shear stress)-mediated dilation (FMD) and vascular wall remodelling are decreased, suggesting a low capacity of the vasculature to adapt to metabolic needs.

OBJECTIVE AND DESIGN:

We assessed the capacity of a systemic vasodilator treatment to improve vascular remodelling and blood flow in mdx mice. We measured vascular structure and function in mesenteric resistance arteries (MRA) from control and mdx mice treated for 1 month with hydralazine.

RESULTS:

Although hydralazine did not significantly affect blood pressure, mesenteric blood flow was increased in control and mdx mice (150+/-25 to 194+/-30 and 110+/-26 to 143+/-18 microl/min; respectively; n=10/group). MRA (90 microm internal diameter, 75 mmHg) were isolated in vitro in arteriographs. Arterial diameter and FMD were significantly increased by hydralazine in control but not in mdx mice. Hydralazine also increased N-nitro-L-arginine methyl ester (L-NAME)-sensitive FMD in control mice, not in mdx mice. Pressure-, phenylephrine-, serotonin- and calcium-induced contraction, as well as acetylcholine- and sodium nitroprusside-induced dilation, were not affected by hydralazine whatever the strain.

CONCLUSION:

This study provides functional evidence that local blood flow could be improve by hydralazine in mdx mice despite a lack of vascular adaptation to flow. This study brings a new insight in the pathophysiology of dystrophin-related myopathies. Nevertheless, the consequences of an increased blood flow in non-adapted arteries remain unknown.

• Authors: Laurent Loufrani, Daniel Henrion
• Journal: Journal of hypertension (J Hypertens) Vol. 23 Issue 10 Pg. 1855-60 (Oct 2005) ISSN: 0263-6352 [Print] England
• PMID: 16148609 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dystrophin
• Enzyme Inhibitors
• Vasoconstrictor Agents
• Vasodilator Agents
• Nitroprusside
• Phenylephrine
• Hydralazine
• Serotonin
• Nitric Oxide Synthase
• Acetylcholine
• Calcium
• NG-Nitroarginine Methyl Ester

Topics

• Acetylcholine (pharmacology)
• Animals
• Blood Flow Velocity (drug effects)
• Blood Pressure
• Body Weight
• Calcium (pharmacology)
• Dystrophin (genetics)
• Endothelium, Vascular (physiology)
• Enzyme Inhibitors (pharmacology)
• Hydralazine (administration & dosage, pharmacology)
• In Vitro Techniques
• Male
• Mesenteric Arteries (drug effects, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred mdx
• Mutation
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitroprusside (pharmacology)
• Phenylephrine (pharmacology)
• Serotonin (pharmacology)
• Stress, Mechanical
• Vascular Resistance
• Vasoconstriction (drug effects)
• Vasoconstrictor Agents (pharmacology)
• Vasodilation (drug effects)
• Vasodilator Agents (administration & dosage, pharmacology)