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

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.

Effect of age on insulin-induced endothelin release and vasoreactivity in hypertriglyceridemic and hypertensive rats.

In the present paper, the age-related changes in the vasoconstrictive endothelin-mediated response to insulin in aortas of normal and hypertensive, hypertriglyceridemic, hyperinsulinemic (HTG) rats were studied. To develop HTG rats, weanling male Wistar animals were given 30% sucrose in their drinking water for 4, 6, 12 and 18 months. Blood pressure was increased in HTG rats for up to 12 months showing a maximum at 6 months (138.9+/-0.8 mmHg). In vitro contractions were elicited with 40 mM KCl in the presence and absence 50 microU/ml insulin and of endothelin-receptor antagonists BQ123 and BQ788. Tension development to KCl was not modified during aging in control rats but was increased at 4 and 6 months in HTG rats. Increased endothelin release induced by insulin remained constant in normal rats, while in HTG rats it was higher than in controls at all ages. ET(A) blocker participation alone increased during aging in control rats while both receptor blockers participated in HTG rats. Our results suggest that the vasoconstrictive capacity to KCl plus insulin decreases during aging and that this decrease is greater in HTG rats. The participation of endothelin receptors in the aging process differs in control and HTG rats.