A ROLE OF MYOFILAMENT CA2+ SENSITIVITY IN ENHANCED VASCULAR REACTIVITY IN CARDIOMYOPATHIC HAMSTERS

We compared the contractile responses to vasoconstrictors in aortas fr om 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, angiotens in 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-dibuty rate (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 staurospo rine and calphostin C than was that of control aorta. These results su ggest that activation of protein kinase C is partly involved in the en hanced phenylephrine response of cardiomyopathic aorta. None of nifedi pine, ryanodine, and cyclopiazonic acid modified the maximum contracti ons induced by phenylephrine in either cardiomyopathic aortas or contr ols. The Ca2+ sensitivity of tension was significantly increased in be ta-escin-skinned smooth muscle of mesenteric artery from cardiomyopath ic hamsters compared to that of controls. PDB induced Ca2+ sensitizati on, but significantly only in cardiomyopathic hamsters. We propose tha t the enhanced vascular reactivity in cardiomyopathic hamsters may pri marily 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. (C) 1998 El sevier Science B.V. All rights reserved.