Senescent murine femoral arteries undergo vascular remodelling associated with accelerated stress‐induced contractility and reactivity to nitric oxide

This work explored the mechanism of augmented stress‐induced vascular reactivity of senescent murine femoral arteries (FAs). Mechanical and pharmacological reactivity of young (12–25 weeks, y‐FA) and senescent (>104 weeks, s‐FAs) femoral arteries was measured by wire myography. Expression and protein phosphorylation of selected regulatory proteins were studied by western blotting. Expression ratio of the Exon24 in/out splice isoforms of the regulatory subunit of myosin phosphatase, MYPT1 (MYPT1‐Exon24 in/out), was determined by polymerase chain reaction (PCR). While the resting length–tension relationship showed no alteration, the stretch‐induced‐tone increased to 8.3 ± 0.9 mN in s‐FA versus only 4.6 ± 0.3 mN in y‐FAs. Under basal conditions, phosphorylation of the regulatory light chain of myosin at S19 was 19.2 ± 5.8% in y‐FA versus 49.2 ± 12.6% in s‐FA. Inhibition of endogenous NO release raised tone additionally to 10.4 ± 1.2 mN in s‐FA, whereas this treatment had a negligible effect in y‐FAs (4.8 ± 0.3 mN). In s‐FAs, reactivity to NO donor was augmented (pD2 = −4.5 ± 0.3 in y‐FA vs. ‐5.2 ± 0.1 in senescent). Accordingly, in s‐FAs, MYPT1‐Exon24‐out‐mRNA, which is responsible for expression of the more sensitive to protein‐kinase G, leucine‐zipper‐positive MYPT1 isoform, was increased. The present work provides evidence that senescent murine s‐FA undergoes vascular remodelling associated with increases in stretch‐activated contractility and sensitivity to NO/cGMP/PKG system.