Modulatory role of a constitutively active population of alpha(1D)-adrenoceptors in conductance arteries.
A constitutively active population of alpha(1D)-adrenoceptors in iliac and proximal, distal, and small mesenteric rat arteries was studied. The increase in resting tone (IRT) that evidences it was observed only in iliac and proximal mesenteric and was inhibited by prazosin (pIC(50) = 9.57), 5-methylurapidil (pIC(50) = 7.61), and BMY 7378 (pIC(50) = 8.77). Chloroethylchlonidine (100 micromol/l) did not affect IRT, but when added before the other antagonists it blocked their effect. The potency shown by BMY 7378 confirms the alpha(1D)-subtype as responsible for IRT. BMY 7378 displayed greater inhibition of adrenergic responses in iliac (pIC(50) = 7.57 +/- 0.11) and proximal mesenteric arteries (pIC(50) = 8.05 +/- 0.2) than in distal (pIC(50) = 6.94 +/- 0.13) or small mesenteric arteries (pIC(50) = 6.30 +/- 0.14), which confirms the functional role of the alpha(1D)-adrenoceptor in iliac and proximal mesenteric arteries. This subtype prevents abrupt changes in iliac and proximal mesenteric artery caliber when the agonist disappears, and this modulatory role is evidenced by the slower decay in the response to norepinephrine after removal.
Ziani
Khalid
K
Departamento de Farmacología, Facultad de Farmacia, Universitat de València, 46100 Burjassot, Valencia, Spain.
Gisbert
Regina
R
Noguera
Maria Antonia
MA
Ivorra
Maria Dolores
MD
D'Ocon
Pilar
P
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001158:Arteries / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007083:Iliac Artery / Q000378:metabolism; D008638:Mesenteric Arteries / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C057446:5-methylurapidil; C051731:chlorethylclonidine; C053428:BMY 7378; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin