Calcitonin gene-related peptide mediates acetylcholine-induced endothelium-independent vasodilation in mesenteric resistance blood vessels of the rat.
The role of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves in acetylcholine chloride (ACh)-induced vasodilation was studied in the perfused mesenteric vascular bed isolated from the rat. Bolus infusions of ACh at smaller doses (0.1 and 1 nmol) produced rapid and short-lived vasodilation. However, larger doses (10 and 100 nmol) of ACh caused a rapid and subsequent long-lasting vasodilator response in which the duration of vasodilation was prolonged in a concentration-dependent manner. Pretreatment with capsaicin (1 mumol/L for 20 minutes) significantly shortened the duration of vasodilator response to ACh but did not affect the initial rapid phase of ACh-induced vasodilation. Chemical removal of the vascular endothelium by perfusion with sodium deoxycholate (1.75 to 1.80 mg/mL) for 30 seconds and subsequent treatment with N omega-nitro-L-arginine (100 mumol/L) to inhibit nitric oxide synthesis abolished the initial rapid vasodilator action of ACh at any given concentration. However, in the same preparation, increasing concentrations (from 1 to 1000 nmol) of ACh produced only the long-lasting vasodilator responses in a concentration-dependent manner. This long-lasting vasodilator response to ACh infusion was abolished by capsaicin pretreatment (1 mumol/L), human CGRP[8-37] (CGRP receptor antagonist, 1 mumol/L), and atropine (muscarinic ACh receptor antagonist, 1, 10, and 100 nmol/L) but not by hexamethonium (nicotinic ACh receptor antagonist, 1 and 10 mumol/L). In the preparations without endothelium, the bolus infusion of ACh (300 nmol for 30 seconds) evoked a long-lasting vasodilation and release of CGRP-like immunoreactivities into the perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)
Takenaga
M
M
First Department of Internal Medicine, Miyazaki Medical College, Japan.
Kawasaki
H
H
Wada
A
A
Eto
T
T
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D018738:Hexamethonium / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects; D014655:Vascular Resistance; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D011976:Receptors, Muscarinic; D003840:Deoxycholic Acid; D018738:Hexamethonium; D001285:Atropine; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine; D002211:Capsaicin