Ex vivo aortic stiffness in mice with different eNOS activity.

An important physiological role of the aorta is to convert the pulsatile blood flow that originates in the heart to a nearly-continuous flow in the peripheral vessels. Previously, we demonstrated that basal, unstimulated NO production is more abundant in large as compared to muscular arteries and that it is an important regulator of arterial (aortic) stiffness. Hence, endothelial function and NO bioavailability are important determinants of aortic biomechanics and mouse models with altered NO signaling might be of interest to investigate the (patho)physiological role of the NO signaling as a dynamic regulator of arterial stiffness. We aimed to characterize the ex vivo biomechanical properties of aortic segments from mice with no (eNOS(-/-)), normal (WT) or high (eNOS-tg) endothelial NO synthase (eNOS) expression. Isobaric aortic diameter and compliance were lower in eNOS(-/-) mice and increased in eNOS-tg mice as compared to WT mice. Interestingly, these differences remained when NO levels were pharmacologically restored, indicating that they were not merely the result of a lack or excess of the vasodilator effects of NO. Analysis of basal vascular smooth muscle cell tone and the phasic as well as the tonic contraction in response to alpha1-adrenergic stimulation with phenylephrine revealed that the chronic lack of eNOS expression affected aortic reactivity similarly but with different magnitude as compared to acute eNOS blockade using L-NAME in WT and eNOS-tg mice, suggesting that chronical distortion of NO signaling triggered several compensatory mechanisms that reflect the organism's attempt to restore the contractile imbalance and maintain optimal central hemodynamics.