Ageing alters perivascular nerve function of mouse mesenteric arteries in vivo

Mesenteric arteries (MAs) are studied widely in vitro but little is known of their reactivity in vivo. Transgenic animals have enabled Ca2+ signalling to be studied in isolated MAs but the reactivity of these vessels in vivo is undefined. We tested the hypothesis that ageing alters MA reactivity to perivascular nerve stimulation (PNS) and adrenoreceptor (AR) activation during blood flow control. First- (1A), second- (2A) and third-order (3A) MAs of pentobarbital-anaesthetized Young (36 months) and Old (2426 months) male and female Cx40BAC-GCaMP2 transgenic mice (C57BL/6 background; positive or negative for the GCaMP2 transgene) were studied with intravital microscopy. A segment of jejunum was exteriorized and an MA network was superfused with physiological salt solution (pH 7.4, 37 degrees C). Resting tone was 10% in MAs of Young and Old mice; diameters were approximate to 5% (1A), 20% (2A) and 40% (3A) smaller (P 0.05) in Old mice. Throughout MA networks, vasoconstriction increased with PNS frequency (116 Hz) but was approximate to 20% less in Young vs. Old mice (P 0.05) and was inhibited by tetrodotoxin (1 m). Capsaicin (10 m; to inhibit sensory nerves) enhanced MA constriction to PNS (P 0.05) by approximate to 20% in Young but not Old mice. Phenylephrine (an 1AR agonist) potency was greater in Young mice (P 0.05) with similar efficacy (approximate to 60% constriction) across ages and MA branches. Constrictions to UK14304 (an 2AR agonist) were less (approximate to 20%; P 0.05) and were unaffected by ageing. Irrespective of sex or transgene expression, ageing consistently reduced the sensitivity of MAs to 1AR vasoconstriction while blunting the attenuation of sympathetic vasoconstriction by sensory nerves. These findings imply substantive alterations in splanchnic blood flow control with ageing.