Ageing alters perivascular nerve function of mouse mesenteric arteries in vivo


  • Erika B. Westcott,

    1. Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA
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  • Steven S. Segal

    1. Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA
    2. Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO 65211, USA
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S. S. Segal: Department of Medical Pharmacology and Physiology, MA415 Medical Sciences Building – 1 Hospital Drive, University of Missouri, Columbia, MO 65212. Email:

Key points

  • Neural control of the circulation is integral to the regulation of tissue blood flow and systemic blood pressure. Vascular dysfunction occurs with ageing but little is known of corresponding changes in the role(s) of perivascular nerves.

  • We developed a preparation to study intact mesenteric arteries (MAs) in anaesthetized mice to investigate age-related changes in the function of perivascular sympathetic and sensory nerves in vivo.

  • Ageing decreased the diameter of MAs, reduced their sensitivity to α1-adrenoreceptor stimulation and impaired the ability of sensory nerves to attenuate sympathetic vasoconstriction.

  • These changes were manifest in males and females and were unaffected by the expression of the GCaMP2 transgene in endothelial cells, confirming the utility of this model.

  • Our results imply that ageing imposes structural and functional limitations to the splanchnic circulation that impair the ability to mobilize blood from the gut in times of physical stress.

Abstract  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 (3–6 months) and Old (24–26 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°C). Resting tone was ≤ 10% in MAs of Young and Old mice; diameters were ∼5% (1A), 20% (2A) and 40% (3A) smaller (P≤ 0.05) in Old mice. Throughout MA networks, vasoconstriction increased with PNS frequency (1–16 Hz) but was ∼20% less in Young vs. Old mice (P≤ 0.05) and was inhibited by tetrodotoxin (1 μm). Capsaicin (10 μm; to inhibit sensory nerves) enhanced MA constriction to PNS (P≤ 0.05) by ∼20% in Young but not Old mice. Phenylephrine (an α1AR agonist) potency was greater in Young mice (P≤ 0.05) with similar efficacy (∼60% constriction) across ages and MA branches. Constrictions to UK14304 (an α2AR agonist) were less (∼20%; P≤ 0.05) and were unaffected by ageing. Irrespective of sex or transgene expression, ageing consistently reduced the sensitivity of MAs to α1AR vasoconstriction while blunting the attenuation of sympathetic vasoconstriction by sensory nerves. These findings imply substantive alterations in splanchnic blood flow control with ageing.