Perivascular Adipose Tissue Modulation of Neurogenic Vasorelaxation of Rat Mesenteric Arteries

Perivascular sympathetic-sensory interactions have been shown to regulate calcitonin gene-related peptide (CGRP)-mediated vasodilation in rats. We investigated whether perivascular adipose tissue (PVAT) modulates the neurogenic vasorelaxation of isolated rat mesenteric arteries. Mesenteric arterial rings were prepared with or without PVAT (PVAT+ or PVAT-) and with either an intact or denuded endothelium (EC+ or EC-). The results of myography analysis revealed that vasocontraction to phenylephrine was highest in EC-PVAT-, lowest in EC+PVAT+, and intermediate in EC-PVAT+ and EC+PVAT-. Transmural nerve stimulation (TNS) induced the tetrodotoxin-sensitive relaxation of the phenylephrine-precontracted mesenteric arteries. However, nicotine induced minor relaxation in EC-PVAT+, whereas vasorelaxation was significantly enhanced in EC-PVAT-. Nicotine-induced vasorelaxation was insensitive to propranolol and also significantly lower in sympathetically-denervated and guanethidine-treated EC-PVAT-, whereas TNS-induced vasorelaxation persisted. In EC-PVAT- depleted of CGRP via capsaicin, nicotine- and TNS-induced vasorelaxation was almost absent. Lowering the pH of Krebs' solution using HCl led to pH-dependent vasorelaxation that was sensitive to CGRP8-37. Furthermore, nicotine-induced relaxation of EC-PVAT-, which was not affected by leptin, was blocked by methyl palmitate. Methyl palmitate did not affect TNS- or HCl-induced vasorelaxation. These results suggest that PVAT plays a modulatory role in regulating sympathetic-sensory interaction-mediated CGRPergic vasorelaxation via the release of methyl palmitate.