Neuropeptide Y and neurovascular control in skeletal muscle and skin

Abstract

Neuropeptide Y (NPY) is a ubiquitous peptide with multiple effects on energy metabolism, reproduction, neurogenesis, and emotion. In addition, NPY is an important sympathetic neurotransmitter involved in neurovascular regulation. Although early studies suggested that the vasoactive effects of NPY were limited to periods of high stress, there is growing evidence for the involvement of NPY on baseline vasomotor tone and sympathetically evoked vasoconstriction in vivo in both skeletal muscle and the cutaneous circulation. In Sprague-Dawley rat skeletal muscle, Y(1)-receptor activation appears to play an important role in the regulation of basal vascular conductance, and this effect is similar in magnitude to the alpha(1)-receptor contribution. Furthermore, under baseline conditions, agonist and receptor-based mechanisms for Y(1)-receptor-dependent control of vascular conductance in skeletal muscle are greater in male than female rats. In skin, there is Y(1)-receptor-mediated vasoconstriction during whole body, but not local, cooling. As with the NPY system in muscle, this neural effect in skin differs between males and females and in addition, declines with aging. Intriguingly, skin vasodilation to local heating also requires NPY and is currently thought to be acting via a nitric oxide pathway. These studies are establishing further interest in the role of NPY as an important vasoactive agent in muscle and skin, adding to the complexity of neurovascular regulation in these tissues. In this review, we focus on the role of NPY on baseline vasomotor tone in skeletal muscle and skin and how NPY modulates vasomotor tone in response to stress, with the aim of compiling what is currently known, while highlighting some of the more pertinent questions yet to be answered.

Fig. 1.

A: representative responses of arterial blood pressure and hindlimb blood flow for each of the N²-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-d-arginine amide (BIBP3226), prazosin, and BIBP3226 + prazosin treatments. The bold arrow represents the time at which infusion of the respective drug (indicated above arrow) was given. The white trace indicates mean hindlimb blood flow for each treatment. Note the increase in diastolic blood flow only when BIBP3226 was present. B: mean changes (Δ) from baseline for hindlimb blood flow (left) and vascular conductance (right) with each treatment. Values represent means ± SE. *P < 0.05, significant difference from baseline; †P < 0.05, significant difference from BIBP3226 and prazosin conditions. [From Jackson et al. (46).].

Fig. 2.

Average responses in cutaneous vascular conductance (CVC) as a percentage of baseline (means ± SE) from skin sites treated with Ringer solution; yohimbine plus propranolol; or yohimbine, propranolol, and BIBP3226 during whole body cooling in eight healthy men. *Significant reduction from baseline (P < 0.05). At sites treated with yohimbine, propranolol, and BIBP-3226, CVC was not significantly reduced at any point in this cooling protocol (P > 0.05). These data indicate the vasomotor response to whole body cooling is mediated largely, if not entirely, by norepinephrine and NPY. P values indicate significant differences in the response between Ringer solution and yohimbine plus propranolol (P < 0.001) and between yohimbine plus propranolol plus BIBP3236 and the other two sites (P < 0.01). [From Stephens et al. (96).]

Fig. 3.

Data from a representative subject showing axon reflexes were either offset to a higher local temperature, as in this case, or were abolished at the YOH/PRO and BIBP-3226 sites. They were uniformly abolished at sites treated with the combination of YOH, PRO, and BIBP-3226. Importantly, note the reduced responses in CVC at all treated sites. Arrows indicate the presence of an axon reflex. [From Hodges et al. (43).]