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

Clin Interv Aging. 2020 Apr 20:15:537-545. doi: 10.2147/CIA.S236173. eCollection 2020.

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.

MeSH terms

  • Aging / pathology*
  • Animals
  • Aorta / pathology*
  • Carotid Intima-Media Thickness
  • Endothelium, Vascular / pathology*
  • Male
  • Muscle Contraction / physiology
  • Muscle, Smooth, Vascular / pathology*
  • Phenylephrine / metabolism
  • Rabbits

Substances

  • Phenylephrine