Depressed perivascular sensory innervation of XXXX mesenteric arteries with advanced age.

@entity2997 @entity455 @entity2951 @entity19 @entity3009 @entity63239 @entity842 @entity3451 @entity3352 @entity12819 @entity1063 @entity6462 @entity4149 @entity393
KEY POINTS: The dilatory role for sensory innervation of mesenteric arteries (MAs) is impaired in Old (   24  months) versus Young (   4  months) @entity19 . We investigated the nature of this impairment in isolated pressurized MAs. With perivascular sensory nerve stimulation, dilatation and inhibition of sympathetic vasoconstriction observed in Young MAs were lost in Old MAs along with impaired dilatation to @entity12819 ( @entity12819 ). Inhibiting NO and @entity3009 synthesis increased @entity12819 EC50 in Young and Old MAs. Endothelial denudation attenuated dilatation to @entity12819 in Old MAs yet enhanced dilatation to @entity12819 in Young MAs while abolishing all dilatations to @entity3451 . In Old MAs, sensory nerve density was reduced and @entity63239 ( @entity12819 receptor component) associated with nuclear regions of endothelial cells in a manner not seen in Young MAs or in smooth muscle cells of either age. With advanced age, loss of dilatory signalling mediated through perivascular sensory nerves may compromise perfusion of visceral organs. ABSTRACT: @entity455 and sympathetic nerve activity increase with advancing age. In the gut, blood flow is governed by perivascular sensory and sympathetic nerves but little is known of how their functional role is affected by advanced age. We tested the hypothesis that functional sensory innervation of mesenteric arteries (MAs) is impaired for Old (24  months) versus Young (4  months) C57BL/6 male @entity19 . In cannulated pressurized MAs preconstricted 50% with @entity1063 and treated with @entity2997 (to inhibit sympathetic neurotransmission), perivascular nerve stimulation (PNS) evoked dilatation in Young but not Old MAs while dilatations to @entity3451 were not different between age groups. In Young MAs, @entity2951 (to inhibit sensory neurotransmission) blocked dilatation and increased constriction during PNS. With no difference in efficacy, the EC50 of @entity12819 as a vasodilator was    6-fold greater in Old versus Young MAs. Inhibiting @entity842 ( @entity6462 ) and @entity3009 ( @entity3352 ) synthesis increased @entity12819 EC50 in both age groups. Endothelial denudation reduced the efficacy of dilatation to @entity12819 by    30% in Old MAs yet increased this efficacy    15% in Young MAs while all dilatations to @entity3451 were abolished. Immunolabelling revealed reduced density of sensory ( @entity12819 ) but not sympathetic ( @entity4149 hydroxylase) innervation for Old versus Young MAs. Whereas the distribution of @entity12819 receptor proteins was similar in SMCs, @entity63239 associated with nuclear regions of endothelial cells of Old but not Young MAs. With advanced age, the @entity393 and diminished effectiveness of @entity12819 as a vasodilator is multifaceted and may adversely affect splanchnic perfusion.
