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  • Title: Estrogen selectively increases sensory nociceptor innervation of arterioles in the female rat.
    Author: Blacklock AD, Cauveren JA, Smith PG.
    Journal: Brain Res; 2004 Aug 20; 1018(1):55-65. PubMed ID: 15262205.
    Abstract:
    Differences exist in vascular function and disease susceptibility in males and females, and estrogen is apparently a primary factor. One mechanism by which estrogen may influence vascular function is by affecting vasomotor innervation. We have shown previously that estrogen increases calcitonin gene-related peptide (CGRP)-immunoreactive sensory innervation of the rat mammary gland, but it is not known if this occurs in other tissues. The objective of this study was to determine if estrogen modulates CGRP-immunoreactive innervation of vascular and non-vascular tissues. Ovariectomized adult virgin female rats were implanted with pellets containing 17beta-estradiol or placebo. After 7 days, innervation was examined in the external ear, jejunal mesenteric arterioles, superficial epigastric, femoral, and uterine arteries, and foot skin. Immunofluorescence microscopy of the external ear pinna revealed increased CGRP-immunoreactive sensory innervation in estrogen-treated rats, and this was attributable specifically to increased innervation of arterioles. Tyrosine hydroxylase-immunoreactive innervation was unchanged. Total nerve density, revealed by the pan-neuronal marker PGP 9.5, was also greater after estrogen treatment, implying structural proliferation of nociceptor vasodilator fibers. Mesenteric arteriolar CGRP-immunoreactive nerve density was also selectively increased by estrogen treatment. However, estrogen did not affect CGRP-immunoreactive nerve density of superficial epigastric, femoral, or uterine arteries, or foot skin. Therefore, estrogen increases sensory innervation of arterioles, but not of large arteries or skin. We conclude that sensory nociceptor vasodilatory innervation of arterioles is selectively enriched by estrogen, which may influence cardiovascular function in health and disease.
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