title: A role of myofilament Ca2+ sensitivity in enhanced vascular reactivity in cardiomyopathic hamsters.
abstract: We compared the contractile responses to vasoconstrictors in aortas from 20- to 22-week old cardiomyopathic hamsters, BIO 53.58 strain, and age-matched F1b strain controls. Aortas from cardiomyopathic hamsters exhibited greater contractions in response to phenylephrine, angiotensin II, and high K+ than did the controls. Neither endothelium removal nor the presence of indomethacin and N(omega)-nitro-L-arginine (L-NNA) affected the enhanced contractile responses to these vasoconstrictors, indicating no involvement of endogenous prostanoids and nitric oxide from the endothelium. The contractile response to phorbol-12,13-dibutyrate (PDB) was also more markedly increased in cardiomyopathic aortas regardless of whether extracellular Ca2+ was present. The contractile response of cardiomyopathic aorta to phenylephrine was more sensitive to the inhibitory actions of the protein kinase C inhibitors staurosporine and calphostin C than was that of control aorta. These results suggest that activation of protein kinase C is partly involved in the enhanced phenylephrine response of cardiomyopathic aorta. None of nifedipine, ryanodine, and cyclopiazonic acid modified the maximum contractions induced by phenylephrine in either cardiomyopathic aortas or controls. The Ca2+ sensitivity of tension was significantly increased in beta-escin-skinned smooth muscle of mesenteric artery from cardiomyopathic hamsters compared to that of controls. PDB induced Ca2+ sensitization, but significantly only in cardiomyopathic hamsters. We propose that the enhanced vascular reactivity in cardiomyopathic hamsters may primarily result from increased Ca2+ sensitivity of contractile proteins. In addition, protein kinase C-mediated Ca2+ sensitization may further contribute to the enhanced vascular response to agonists.
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Hattori
authors.forename: M
authors.initials: M
authors.lastname: Fukao
authors.forename: M
authors.initials: M
authors.lastname: Kanno
authors.forename: I
authors.initials: I
authors.lastname: Sakuma
authors.forename: A
authors.initials: A
authors.lastname: Kitabatake
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D009202:Cardiomyopathies / Q000378:metabolism / Q000503:physiopathology*; D006224:Cricetinae; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009281:Naphthalenes / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D007211:Indoles; D009281:Naphthalenes; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D012433:Ryanodine; D010656:Phenylephrine; D015240:Phorbol 12,13-Dibutyrate; D019311:Staurosporine; C058819:calphostin C; D009543:Nifedipine; D011188:Potassium; D002118:Calcium; C000543:cyclopiazonic acid