Effect of clofibrate on vascular reactivity in a model of high blood pressure secondary to aortic coarctation.

Abstract

The aims of this study were to identify the effect of clofibrate administration in the development of high blood pressure secondary to aortic coarctation (AoCo) and to assess its effect on vascular reactivity. Three experimental groups of rats were used: sham-operated, aortic coarctated vehicle-treated (AoCo-V), and aortic coarctated clofibrate-treated (AoCo-C100). The rats were treated for seven days. Blood pressure was measured, and the vascular response to angiotensin II (AngII), norepinephrine (NE), and acetylcholine (ACh) were evaluated in aortic rings. The activity and expression of endothelial nitric oxide synthase (eNOS) was also evaluated. The major findings of this study include the following: AoCo induced a rise in blood pressure, and this effect was attenuated by clofibrate. The vascular response to AngII was higher in aortic rings from the AoCo-V group compared to the Sham-V or AoCo-C100 groups. ACh-elicited vasorelaxation was lower in the arteries of AoCo-V rats than Sham-V or AoCo-C100, while it was comparable between the Sham-V and AoCo-C100 groups. In every case, vasorelaxation was dependent on NO. However, the ACh-induced release of NO as well as NOS activity and expression were reduced in the arteries of AoCo-V rats. Clofibrate maintained normal NOS activity and increased eNOS expression. In conclusion, clofibrate administration attenuated the AoCo-induced rise in blood pressure by a mechanism that involves the participation of the NO system at both the NO synthesis and the eNOS protein expression levels. These events improved endothelial function, preserved normal vascular responses to both vasorelaxants and vasoconstrictors, and led to better blood pressure control.

• Authors: Luz Graciela Cervantes-Pérez, María Luz Ibarra-Lara, María Esther Rubio, Bruno Escalante, Francisca Pérez-Severiano, Elizabeth Soria-Castro, Margarita Carmen Ramírez-Ortega, María Alicia Sánchez-Mendoza
• Journal: Pharmacological reports : PR (Pharmacol Rep) 2010 Sep-Oct Vol. 62 Issue 5 Pg. 874-82 ISSN: 2299-5684 [Electronic] Switzerland
• PMID: 21098870 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hypolipidemic Agents
• Vasoconstrictor Agents
• Vasodilator Agents
• Angiotensin II
• Nitric Oxide
• Nitric Oxide Synthase Type III
• Clofibrate
• Acetylcholine
• Norepinephrine

Topics

• Acetylcholine (pharmacology)
• Angiotensin II (pharmacology)
• Animals
• Aortic Coarctation (complications)
• Clofibrate (pharmacology, therapeutic use)
• Endothelium, Vascular (drug effects, physiopathology)
• Hypertension (etiology, physiopathology, prevention & control)
• Hypolipidemic Agents (pharmacology, therapeutic use)
• In Vitro Techniques
• Male
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type III (metabolism)
• Norepinephrine (pharmacology)
• Rats
• Rats, Wistar
• Vasoconstrictor Agents (metabolism, pharmacology)
• Vasodilation (drug effects)
• Vasodilator Agents (pharmacology)