title: Norepinephrine elicits beta2-receptor-mediated dilation of isolated human coronary arterioles.
abstract: BACKGROUND
  The exact role of adrenoceptors in norepinephrine (NE)-mediated regulation of the human coronary circulation has yet to be elucidated. Thus, the goals of this study were to characterize the adrenoceptors involved in the responses to NE in isolated human coronary arterioles and small arteries.
  
  
  RESULTS
  Arterioles (n=39) and small arteries from the left ventricle of explanted human hearts were isolated and cannulated. Vessels from the hearts of 21 patients were studied: 15 males and 6 females, aged 0.5 to 63 years. Nineteen patients were considered to be New York Heart Association class 4. All hearts exhibited hypertrophy (190+/-20%). The passive diameter of arterioles was 167+/-8 microm (range 97 to 323 microm). NE (10(-7) to 3x10(- 7) mol/L) elicited concentration-dependent dilations (47+/-4 microm) that were unaffected by endothelium removal, N(omega)-nitro-L-arginine (10(- 4) mol/L, an NO synthase inhibitor), or practolol (10(-6) mol/L, a beta1-receptor blocker). However, administration of propranolol (10(-5) mol/L, a combined beta1- and beta2-blocker) or butoxamine (10(-6) mol/L, a beta2-receptor blocker) completely eliminated the NE-induced dilation. Constrictions to NE (2 of 39 vessels) were inhibited by prazosin (10(-6) mol/L, an alpha1-receptor blocker). Methoxamine (10(-9) to 10(-5) mol/L, an alpha1-agonist) had no effect, whereas U44619, a thromboxane mimetic, elicited dose-dependent constriction of vessels.
  
  
  CONCLUSIONS
  Our data indicate that isolated human coronary arterioles and small arteries dilate to NE via beta2-receptors on smooth muscle. These findings are important to our understanding of the mechanisms action of NE in the human coronary circulation.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla 10595, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Sun
authors.forename: An
authors.initials: A
authors.lastname: Huang
authors.forename: Seema
authors.initials: S
authors.lastname: Mital
authors.forename: Maryanne R
authors.initials: MR
authors.lastname: Kichuk
authors.forename: Charles C
authors.initials: CC
authors.lastname: Marboe
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Addonizio
authors.forename: Robert E
authors.initials: RE
authors.lastname: Michler
authors.forename: Akos
authors.initials: A
authors.lastname: Koller
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hintze
authors.forename: Gabor
authors.initials: G
authors.lastname: Kaley
mesh_terms: D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D001160:Arterioles / Q000187:drug effects* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006331:Heart Diseases / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D014654:Vascular Patency / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D018343:Receptors, Adrenergic, beta-2; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009638:Norepinephrine