Alpha-adrenergic vasoconstriction and receptor subtypes in large coronary arteries of calves.
We investigated alpha-adrenoceptor subtype distribution in large coronary arteries from both functional and biochemical perspectives. The effects of intracoronary administration of the selective alpha 1-adrenoceptor agonist phenylephrine (0.1-5.0 micrograms/kg ic), of the selective alpha 2-adrenoceptor agonist B-HT 920 (0.1-5.0 micrograms/kg ic), and of the mixed alpha 1 + 2-adrenoceptor agonist norepinephrine (0.01-0.5 micrograms/kg ic) were examined on measurements of left circumflex coronary artery diameter in conscious calves. After beta-adrenergic blockade, equivalent reductions in large coronary artery diameter were observed with phenylephrine (-6.9 +/- 0.7%), B-HT (-5.9 +/- 0.5%), and norepinephrine (-6.0 +/- 0.4%). Phenylephrine-induced constrictions were abolished by prazosin, an alpha 1-selective antagonist, but unaffected by rauwolscine, an alpha 2-selective antagonist. Conversely, the B-HT-induced constriction was abolished by rauwolscine but unaffected by prazosin. Coronary constriction with norepinephrine was attenuated with either prazosin or rauwolscine and abolished by the two antagonists combined. Ligand-binding studies in which [3H]prazosin and [3H]rauwolscine and sarcolemmal membranes were used revealed an alpha 1-adrenoceptor density of 15 +/- 3.1 fmol/mg protein with a dissociation constant (KD) of 0.7 +/- 0.2 nM and an alpha 2-adrenoceptor density of 68 +/- 5.1 fmol/mg protein, with a KD of 7.4 +/- 1.2 nM. Thus large coronary arteries of the calf contain both alpha 1- and alpha 2-adrenoceptor subtypes, each of which elicits constriction of the large coronary artery in the conscious animal.
Young
M A
MA
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.
Vatner
D E
DE
Knight
D R
DR
Graham
R M
RM
Homcy
C J
CJ
Vatner
S F
SF
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D012016:Reference Values; D014661:Vasoconstriction / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D015016:Yohimbine; C024763:talipexole; D009638:Norepinephrine; D011224:Prazosin