Determining the molecular mechanisms of vascular sympathetic innervation

Abstract

Sympathetic nerves regulate blood pressure via peripheral vasoconstriction and redistribution of cardiac output. As some arteries are innervated while others are not, we tested the hypothesis that molecular cues expressed by vessels promote attraction and/or repulsion of sympathetic neurons. In CD1 mice, tyrosine hydroxylase staining shows sympathetic innervation of femoral arteries increases from 52 to 75% of adult innervation densities between birth and 2d postnatal (p<0.01) and was not different from adult by 4d. Using qRT‐PCR, expression profiles of known candidate molecules between innervated femoral and non‐innervated carotid arteries included significant (p<0.01) increases in carotid Sema3a (3X), femoral VEGF (3X) and Sema3f (2X). In addition, their cognate receptors neuropilin‐1, VEGFR2 and neuropilin‐2 are expressed in superior cervical ganglia (SCG). Suppression subtractive hybridization is being used to identify novel candidates. Further, in a 3D collagen gel, average neurite outgrowth from SCG explants towards the femoral is increased by 20% (p<0.01) compared to carotid suggesting that chemorepulsion contributes to lack of carotid innervation. These findings provide evidence of differential expression of axon guidance molecules by innervated and non‐innervated vessels and present an model for investigating selective vascular innervation. R37 HL28373 to JAM, T32 GM07527.