Analysis of responses to hAmylin, hCGRP, and hADM in isolated resistance arteries from the mesenteric vascular bed of the rat.
Responses to human calcitonin gene-related peptide (hCGRP) and human adrenomedullin (hADM) hAmylin were investigated in isolated mesenteric resistance arteries from the rat. The results of the present investigation show that hCGRP, hAmylin, and hADM induce dose-related vasodilator responses in isolated resistance arteries from the rat mesenteric vascular bed. Vasodilator responses to hCGRP and hAmylin were not altered after denuding the vascular endothelium, after administration of the nitric oxide synthase inhibitor L-NA, or after administration of the soluble guanylate cyclase inhibitor ODQ, suggesting that vasodilator responses to hCGRP and hAmylin are not mediated by the release of nitric oxide from the vascular endothelium and the subsequent increase in cGMP. Vasodilator responses to hCGRP, hAmylin, and hADM were not altered by the vascular selective K+(ATP) channel antagonist U-37883A. The role of the CGRP1 receptor was investigated and responses to hCGRP and hAmylin, but not hADM, were significantly reduced following administration of hCGRP-(8-37). Moreover, vasodilator responses to hCGRP and hAmylin, but not hADM, were significantly reduced by hAmylin-(8-37), suggesting that an hAmylin-(8-37)-sensitive receptor mediates responses to hCGRP and hAmylin in the rat mesenteric artery. These data suggest that hCGRP and hAmylin have direct vasodilator effects in the isolated mesenteric resistance artery that are mediated by hAmylin-(8-37)- and hCGRP-(8-37)-sensitive receptors.
Champion
H C
HC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Pierce
R L
RL
Bivalacqua
T J
TJ
Murphy
W A
WA
Coy
D H
DH
Kadowitz
P J
PJ
D000109:Acetylcholine / Q000494:pharmacology; D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D053607:Adrenomedullin; D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D019806:Cromakalim / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010069:Oxadiazoles / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D010477:Perfusion; D026902:Potassium Channel Blockers; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000502:physiology*; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide / Q000187:drug effects / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000682:Amyloid; D004791:Enzyme Inhibitors; D058228:Islet Amyloid Polypeptide; D009025:Morpholines; D010069:Oxadiazoles; D010446:Peptide Fragments; D010455:Peptides; D026902:Potassium Channel Blockers; D011810:Quinoxalines; D018015:Receptors, Calcitonin Gene-Related Peptide; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide; D014665:Vasodilator Agents; D019806:Cromakalim; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; C082658:U 37883A; D001120:Arginine; D019001:Nitric Oxide Synthase; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine; D000218:Adamantane