Influence of Ageing on Vascular Reactivity and Receptor Expression in Rabbit Aorta: A Complement to Elastocalcinosis and Smooth Muscle Mechanisms

摘要

Aim: To contribute to the knowledge about the mechanisms involved in aortic stiffness due to ageing. Materials and Methods: Aortic rings from young (1.5± 0.5 months, 0.8± 0.2 kg), adult (6± 0.5 months, 2.7± 0.5 kg) and old (28± 8 months, 3.2± 0.8 kg) male New Zealand?rabbits were used to evaluate: 1) intima-media thickness by optical microscopy; 2) vascular reactivity (VR) in terms of sensitivity (pD2) and efficacy (Emax) to KCl; phenylephrine (PE); U-46619, a thromboxane A2 receptor agonist, TXA2; carbachol (CCh), isoproterenol and sodium nitroprusside (SNP), using organ bath experiments; and 3) the expression of receptors α 1, β 2 and thromboxane-prostanoids (TP), by immunofluorescence. Results: Ageing 1) did not change the thickness of tunica; 2) significantly reduced the pD2 to KCl, increased the pD2 to PE and reduced both the pD2 and Emax to TXA2, CCh and isoproterenol, and reduced the pD2 to SNP; and 3) significantly increased the expression of α 1 and β 2 receptors in the intima and adventitia, and the expression of TP only in the adventitia. Conclusion: Our results suggest that ageing makes the aorta more reactive to α 1 adrenergic contraction, and it could be a compensation for lower responsiveness to prostanoids. The aged aorta is less reactive to endothelium-dependent and non-dependent relaxation, and the vessel seems to try to compensate for that stiffness increasing β 2 receptors, although probably less functional. These results complement the proposed mechanisms of elastocalcinosis and smooth muscle rigidity, expanding the vision that should guide the treatment of aortic stiffness due to aging.