Universität zu Köln

Lubomirov, Lubomir T., Papadopoulos, Symeon, Puetz, Sandra, Welter, Johannes, Kloeckener, Tim, Weckmueller, Kathrin, Ardestani, Mostafa A., Filipova, Dilyana ORCID: 0000-0003-3532-9765, Metzler, Doris, Metzner, Harald, Staszewski, Juergen, Zittrich, Stefan, Gagov, Hristo, Schroeter, Mechthild M. and Pfitzer, Gabriele (2017). Aging-related alterations in eNOS and nNOS responsiveness and smooth muscle reactivity of murine basilar arteries are modulated by apocynin and phosphorylation of myosin phosphatase targeting subunit-1. J. Cereb. Blood Flow Metab., 37 (3). S. 1014 - 1030. THOUSAND OAKS: SAGE PUBLICATIONS INC. ISSN 1559-7016

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Abstract

Aging causes major alterations of all components of the neurovascular unit and compromises brain blood supply. Here, we tested how aging affects vascular reactivity in basilar arteries from young (<10 weeks; y-BA), old (>22months; o-BA) and old (>22months) heterozygous MYPT1-T-696A/+knock-in mice. In isometrically mounted o-BA, media thickness was increased by approximate to 10% while the passive length tension relations were not altered. Endothelial denudation or pan-NOS inhibition (100 mu mol/L L-NAME) increased the basal tone by 11% in y-BA and 23% in o-BA, while inhibition of nNOS (1 mu mol/L L-NPA) induced approximate to 10% increase in both ages. eNOS expression was approximate to 2-fold higher in o-BA. In o-BA, U46619-induced force was augmented (pEC(50) approximate to 6.9 vs. pEC(50) approximate to 6.5) while responsiveness to DEA-NONOate, electrical field stimulation or nicotine was decreased. Basal phosphorylation of MLC20-S19 and MYPT1-T-853 was higher in o-BA and was reversed by apocynin. Furthermore, permeabilized o-BA showed enhanced Ca2+-sensitivity. Old T-696A/+BA displayed a reduced phosphorylation of MYPT1-T696 and MLC20, a lower basal tone in response to L-NAME and a reduced eNOS expression. The results indicate that the vascular hypercontractility found in o-BA is mediated by inhibition of MLCP and is partially compensated by an upregulation of endothelial NO release.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lubomirov, Lubomir T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Papadopoulos, Symeon UNSPECIFIED UNSPECIFIED UNSPECIFIED Puetz, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Welter, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Kloeckener, Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED Weckmueller, Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Ardestani, Mostafa A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Filipova, Dilyana UNSPECIFIED orcid.org/0000-0003-3532-9765 UNSPECIFIED Metzler, Doris UNSPECIFIED UNSPECIFIED UNSPECIFIED Metzner, Harald UNSPECIFIED UNSPECIFIED UNSPECIFIED Staszewski, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Zittrich, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Gagov, Hristo UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeter, Mechthild M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfitzer, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-238371
DOI:	10.1177/0271678X16649402
Journal or Publication Title:	J. Cereb. Blood Flow Metab.
Volume:	37
Number:	3
Page Range:	S. 1014 - 1030
Date:	2017
Publisher:	SAGE PUBLICATIONS INC
Place of Publication:	THOUSAND OAKS
ISSN:	1559-7016
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHOLINERGIC PREJUNCTIONAL INHIBITION; NITRIC-OXIDE; BLOOD-FLOW; INTERNATIONAL-COOPERATION; PTERYGOPALATINE GANGLION; SPHENOPALATINE GANGLION; CA2+ SENSITIZATION; CEREBRAL-ARTERIES; NERVE-STIMULATION; ISCHEMIC-STROKE Multiple languages Endocrinology & Metabolism; Hematology; Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23837