Effect of short- and long-term heart failure on small artery morphology and endothelial function in the rat

Chronic heart failure (HF) is associated with hemodynamic changes and activ ation of several neurohormonal systems, which are able both to inhibit and to facilitate arterial growth or remodeling and also to influence endotheli al function. As these vascular changes may depend on the duration of HF, we evaluated morphologic and endothelial functional alterations in a rat mode l of HF after a short and long duration of HF. Rats with coronary ligation and sham-operated controls were investigated either 8 or 26 weeks after the operation with measurements of hemodynamics and isolated mesenteric small artery morphology and endothelial function. The effect of HF and duration o f HF were examined by using two-way analysis of variance (ANOVA). HF rats h ad altered hemodynamics with reductions in cardiac output, left ventricular systolic pressure, and mean blood pressure, whereas left ventricular diast olic pressure was increased. HF caused remodeling of anatomically well-defi ned mesenteric small arteries with a reduction in media thickness and media -to-lumen ratio, but without change in the media cross-sectional area. Neit her HF nor time had any influence on sensitivity or maximal relaxation to a cetylcholine in the presence of indomethacin, but HF reduced vasoconstricti on due to nitric oxide synthase blockade with N-G-nitro-L-arginine independ ent of time. Our results indicate that HF, induced by coronary ligation in the rat, has a remodeling effect on mesenteric small arteries. However, the remodeling is moderate compared with that observed in hypertension. Furthe rmore, our results suggest that HF reduces basal release of NO.