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

Abstract

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 α1, β2 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 α1 and β2 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 α1 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 β2 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.

Keywords:

• ageing
• aortic rings
• vascular reactivity
• vascular smooth muscle
• vascular stiffness

Acknowledgments

We want to thank the project “High Level Human Talent Training” approved by the Science, Technology and Innovation Fund (CTeI) of the General Royalty System (SGR)-BPIN 2013000100103, Tolima Governorate and University of Tolima, Colombia; the CODI grants, 2014-University of Antioquia; and the Foundation for the Promotion of Research and Technology, 2017-Bank of the Republic of Colombia.

Disclosure

The authors report no conflicts of interest in this work.