title: Effects of atherosclerosis on the coronary microcirculation.
abstract: We tested the hypothesis that atherosclerosis potentiates coronary vasoconstriction to serotonin and ergonovine. Coronary microvascular pressures and diameters were measured in the beating left ventricle in normal and atherosclerotic cynomolgus monkeys. Pressures were measured in arteries (190-350 microns diam) that were distal to atherosclerotic lesions. Microvascular pressure and simultaneous measurements of aortic pressure and myocardial blood flow were used to calculate segmental vascular resistance (large artery resistance and microvascular resistance) during serotonin, phenylephrine, and ergonovine dosages. Aortic pressure was maintained constant during all interventions. Administration of phenylephrine (50 micrograms.kg-1.min-1 iv) produced a similar increase in microvascular resistance from base line (P less than 0.05) in atherosclerotic and normal animals, 26 +/- 5 and 14 +/- 9 mmHg.min.g.ml-1, respectively. Serotonin (50 micrograms/min) did not influence coronary resistance in normal animals but produced a significant increase in both large artery (8 +/- 3 mmHg.min.g.ml-1) and microvascular resistance (21 +/- 6 mmHg.min.g.ml-1) in atherosclerotic animals (P less than 0.05). A higher dose of serotonin (200 micrograms/min) produced a modest increase in large artery resistance from base line in normal animals (3 +/- 1 mmHg.min.g.ml-1) and a greater increase in atherosclerotic animals (9 +/- 4 mmHg.min.g.ml-1) (P less than 0.05 vs. normals). Ergonovine (10 micrograms.kg-1.min-1 iv) elevated microvascular resistance in both normal and atherosclerotic animals (P less than 0.05) but increased large artery resistance only in atherosclerotic animals (10 +/- 4 mmHg.min.g.ml-1) (P less than 0.05). In summary, coronary vasoconstrictor responses to serotonin and ergonovine were potentiated by atherosclerosis. Because augmented constrictor responses to serotonin were observed in both the diseased arteries and the microcirculation of atherosclerotic animals, we speculate that the pathophysiological consequences of atherosclerosis extend into the microcirculation.
authors.affiliation: Department of Medical Physiology, Texas A&M University College of Medicine, College Station 77843.
authors.forename: W M
authors.initials: WM
authors.lastname: Chilian
authors.forename: K C
authors.initials: KC
authors.lastname: Dellsperger
authors.forename: S M
authors.initials: SM
authors.lastname: Layne
authors.forename: C L
authors.initials: CL
authors.lastname: Eastham
authors.forename: M A
authors.initials: MA
authors.lastname: Armstrong
authors.forename: M L
authors.initials: ML
authors.lastname: Marcus
authors.forename: D D
authors.initials: DD
authors.lastname: Heistad
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000473:pathology; D004874:Ergonovine / Q000494:pharmacology; D006439:Hemodynamics; D008252:Macaca fascicularis; D008833:Microcirculation; D010656:Phenylephrine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014655:Vascular Resistance
chemical_list: D010656:Phenylephrine; D012701:Serotonin; D000241:Adenosine; D004874:Ergonovine