Influence of estradiol supplementation on neuropeptide Y neurotransmission in skeletal muscle arterioles of F344 rats

Abstract

<jats:p>The effects of estradiol on neuropeptide Y (NPY) neurotransmission in skeletal muscle resistance vessels have not been described. The purpose of this study was to determine the effects of long-term estradiol supplementation on NPY overflow, degradation, and vasoconstriction in gastrocnemius first-order arterioles of adult female rats. Female rats (4 mo; n = 34) were ovariectomized (OVX) with a subset ( n = 17) receiving an estradiol pellet (OVE; 17β-estradiol, 4 μg/day). After conclusion of the treatment phase (8 wk), arterioles were excised, placed in a physiological saline solution (PSS) bath, and cannulated with micropipettes connected to albumin reservoirs. NPY-mediated vasoconstriction via a Y<jats:sub>1</jats:sub>-agonist [Leu31Pro34]NPY decreased vessel diameter 44.54 ± 3.95% compared with baseline; however, there were no group differences in EC<jats:sub>50</jats:sub>(OVE: −8.75 ± 0.18; OVX: −8.63 ± 0.10 log M [Leu31Pro34]NPY) or slope (OVE: −1.11 ± 0.25; OVX: −1.65 ± 0.34% baseline/log M [Leu31Pro34]NPY). NPY did not potentiate norepinephrine-mediated vasoconstriction. NPY overflow experienced a slight increase following field stimulation and significantly increased ( P &lt; 0.05) over control conditions in the presence of a DPPIV inhibitor (diprotin A). Estradiol status did not affect DPPIV activity. These data suggest that NPY can induce a moderate decrease in vessel diameter in skeletal muscle first-order arterioles, and DPPIV is active in mitigating NPY overflow in young adult female rats. Long-term estradiol supplementation did not influence NPY vasoconstriction, overflow, or its enzymatic breakdown in skeletal muscle first-order arterioles.</jats:p>

Endogenous dipeptidyl peptidase IV modulates skeletal muscle arteriolar diameter in rats

“…; Evanson et al. , ). Therefore, part of the effect seen with Diprotin A may be from the membrane‐bound DPP‐IV.…”

“…; Evanson et al. , ). It is also expressed on the abluminal surface of blood vessels, where it truncates approximately 40% of the neuropeptide Y (NPY 1‐36 ) released from the sympathetic neurons to become NPY 3‐36 (Evanson et al.…”

“…; Evanson et al. , ). As well, past research illustrates that DPP‐IV activity can be altered chronically by estrogen (Jackson et al., ,b).…”

“…It is also expressed on the abluminal surface of blood vessels, where it truncates approximately 40% of the neuropeptide Y (NPY 1‐36 ) released from the sympathetic neurons to become NPY 3‐36 (Evanson et al. , ). The effect of this enzyme on NPY bioavailability has a profound impact on the relative contribution of adrenergic versus nonadrenergic vasoconstriction in skeletal muscle microcirculation (Jackson et al., ,b).…”

Neural Control of Vascular Function in Skeletal Muscle

“…Complementing this evidence of proximal adrenergic dominance, both NPY (80) and ATP (111) demonstrated peak responses at the distal precapillary terminal arterioles. Other data seem to support the idea of NPY's major role in regulating distal microvasculature (87,141,146). However, these earlier studies are not conclusive because Evanson et al (87) limited their investigation to isolated 1A vessels from rat gastrocnemius muscle, Joshua (146) limited findings to three arteriolar orders in nonlocomotive skeletal muscle (cremaster), and Jackson et al (141) made generalized inferences from bulk blood flow profiles measured at the femoral artery of rats during pharmacological blockade.…”