Universität zu Köln

Lubomirov, Lubomir T., Jaensch, Monique Heidrun, Papadopoulos, Symeon, Schroeter, Mechthild M., Metzler, Doris, Bust, Maria, Hescheler, Juergen, Grisk, Olaf, Ritter, Oliver and Pfitzer, Gabriele (2022). Senescent murine femoral arteries undergo vascular remodelling associated with accelerated stress-induced contractility and reactivity to nitric oxide. Basic Clin. Pharmacol. Toxicol., 130 (1). S. 70 - 84. HOBOKEN: WILEY. ISSN 1742-7843

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Abstract

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 (pD(2) = -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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lubomirov, Lubomir T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaensch, Monique Heidrun UNSPECIFIED UNSPECIFIED UNSPECIFIED Papadopoulos, Symeon UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeter, Mechthild M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Metzler, Doris UNSPECIFIED UNSPECIFIED UNSPECIFIED Bust, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Grisk, Olaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Ritter, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfitzer, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-573430
DOI:	10.1111/bcpt.13675
Journal or Publication Title:	Basic Clin. Pharmacol. Toxicol.
Volume:	130
Number:	1
Page Range:	S. 70 - 84
Date:	2022
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1742-7843
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LIGHT-CHAIN PHOSPHATASE; MEDIATED CA2+ SENSITIZATION; SMOOTH-MUSCLE; MYOSIN PHOSPHATASE; PHOSPHORYLATION SITES; BASILAR ARTERIES; PROTEIN; ISOFORMS; KINASE; VASOCONSTRICTION Multiple languages Pharmacology & Pharmacy; Toxicology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57343