Role of Calcitonin Gene-related Peptide-containing Nerves in the Vascular Adrenergic Neurotransmission

The role of calcitonin gene-related peptide (CGRP)-containing nerves in adrenergic vasoconstrictor response to periarterial nerve stimulation (PNS) was investigated in mesenteric vascular beds isolated from rats, which were perfused with Krebs' solution (5 ml/min). In perfused mesenteric vascular beds, PNS (1-12 Hz, for 30 sec) caused a frequency-dependent increase in the perfusion pressure, which was prevented by 50 nM prazosin and abolished by 300 nM tetrodotoxin and 5 microM guanethidine. Bolus infusion of norepinephrine (NE, 0.5 and 1 nmol) also produced a pressor response which was blocked by 50 nM prazosin. In the preparation treated with 500 nM capsaicin for 20 min, pressor responses to PNS of 1 to 8 Hz were potentiated significantly. The pressor responses to NE infusion also were enhanced in both the preparations treated with and without capsaicin. In the capsaicin-untreated preparation contracted by 7 mM methoxamine in the presence of 5 microM guanethidine, PNS (1-12 Hz) caused a frequency-dependent vasodilation, which was abolished by 300 nM tetrodotoxin. However, no vasodilator response to PNS was observed in the preparation treated with capsaicin. In the contracted preparation, bolus infusion of rat CGRP (10 and 100 pmol) produced a marked long-lasting vasodilation which mimicked the PNS-evoked vasodilation, whereas neither bolus infusion of substance P (1 and 10 nmol), neurokinin A (1 and 10 nmol) nor neurokinin B (1 and 10 nmol) produced relaxation. In the preparation labeled with [3H]NE, the PNS (4 Hz)-evoked 3H release was not altered after capsaicin treatment, whereas the pressor response to PNS was potentiated significantly.(ABSTRACT TRUNCATED AT 250 WORDS)