NPY modulates neurotransmission of CGRP-containing vasodilator nerves in rat mesenteric arteries

Abstract

The effect of neuropeptide Y (NPY) in neurotransmission of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves was investigated in rats. In perfused mesenteric vascular beds with active tone, perivascular nerve stimulation (PNS; 1-8 Hz) caused a frequency-dependent vasodilator response, which was abolished by 300 nM tetrodotoxin (TTX), 500 nM capsaicin, 1 microM human CGRP-(8-37), or cold storage denervation (4 degrees C for 72 h). NPY (5, 10, and 50 nM) concentration dependently inhibited the vasodilator response to PNS, whereas NPY had little effect on vasodilation induced by exogenous CGRP (10 and 100 pmol) or 1 nmol acetylcholine (ACh). NPY (10 nM) inhibited the neurogenic release of CGRP-like immunoreactivity induced by PNS (4 and 8 Hz), which was abolished by 300 nM TTX and the removal of Ca2+ from the medium. Combined perfusion with 5 nM NPY and 10 nM norepinephrine additively inhibited the vasodilator response to PNS but not to exogenous CGRP and ACh. Immunohistochemistry showed the distinct distribution of CGRP- and NPY-like immunoreactivity-containing fibers in rat mesenteric arteries. These results suggest that NPY modulates presynaptically the release of CGRP from CGRP-containing vasodilator nerves in rat mesenteric arteries.

Endogenous calcitonin gene‐related peptide (CGRP) mediates adrenergic‐dependent vasodilation induced by nicotine in mesenteric resistance arteries of the rat

“…Capsaicin has been shown to deplete neuropeptides such as CGRP, substance P and vasoactive intestinal polypeptide (VIP) from primary sensory neurons which leads to depleting capsaicin-sensitive primary nerves (Fujimori et al, 1989;Holzer, 1991). Furthermore, the PNS-induced neurogenic vasorelaxation in the rat mesenteric artery is also inhibited by human CGRP[8 ± 37], a C-terminal fragment of CGRP and a CGRP receptor antagonist, indicating that the vasorelaxation is mediated by endogenous CGRP released from CGRPergic nerves (Kawasaki et al, 1991;Takenaga et al, 1995). In the present study, the vasodilator response to nicotine perfusion was sensitive to the eect of capsaicin.…”

“…Isolated mesenteric vascular beds were stored in cold Krebs solution at 48C for 72 h to achieve cold-storage denervation (Kawasaki et al, 1991). To determine the intact responsiveness of the smooth muscle, a bolus injection of ACh or CGRP was carried out to cause vasodilation.…”

Hyperinsulinemia induces hypertension associated with neurogenic vascular dysfunction resulting from abnormal perivascular innervations in rat mesenteric resistance arteries

“…The vasodilator response to PNS has been shown to be mediated by CGRPergic nerves, since the response was blocked by a CGRP receptor antagonist (CGRP (8-37)) and a CGRP depletor (capsaicin). 16,17 Bolus injections of CGRP at concentrations of 50 and 100 pmol also induced concentration-dependent vasodilation (Figures 3b and d), which has been shown to be mediated by postsynaptic CGRP receptors. 18 Hyperinsulinemia altered perivascular innervation Y Zamami et al Additionally, there was no significant difference in the methoxamine-induced rises in mean perfusion pressure before PNS between control rats (103.1±8.4 mm Hg, n¼8) and FDR (94.7±12.9 mm Hg, n¼7).…”

“…In the rat perfused mesenteric vascular bed precontracted with methoxamine in the presence of guanethidine, the vasodilator response to PNS has been shown to be mediated by the CGRP-containing vasodilator nerve, as the response is blocked by CGRP (8-37), a CGRP receptor antagonist, and capsaicin, which causes CGRP depletion in CGRPergic nerves. 16,17 It seems likely that CGRPergic nerve activity is decreased in mesenteric arteries of FDR. This notion is supported by the present finding that the CGRP content in the DRG of FDR was significantly lower than that in control rats, since the DRG, which contains the cell bodies of CGRPergic nerves, is a prominent site of CGRP synthesis.…”

“…16,17 A prominent site of CGRP synthesis has been shown to be the DRG, which contains the cell bodies of primary afferent neurons that extend CGRPergic nerves to peripheral sites such as blood vessels. 19 In addition to neurogenic vascular responsiveness in the perfused mesenteric vascular beds, to clarify the effect of insulin resistance and chronic hyperinsulinemia on CGRPergic nerves activity, we investigated the content of CGRP in DRG isolated from control rats and FDR by an ELISA.…”