Contribution of the sarcoplasmic reticulum to large artery contractility after myocardial infarction

Mohamed A. Gaballa, Gregory D. Pennock, Steven Goldman

Research output: Contribution to journalArticle

Abstract

Arterial smooth muscle potentiates the elevation in afterload after myocardial infarction (MI) by increasing the dynamic stiffness of large arteries. To examine large artery smooth muscle contractile function after MI, the response to norepinephrine (NE) was studied in de-endothelialized rings from rat ascending aortas, N=8. Maximal developed tension induced by NE at concentrations ≥ 2×10-7 M were higher in MI animals compared to control (P<0.05). At 2×10-5 M NE, time to peak tension was shorter in MI animals compared to control (75±9 vs 138±18 sec, P<0.05). We measured Ca2+-induced contractions in saponin-skinned rings from sham and MI rats. No differences were found between the two groups in Ca2+-dose responses obtained using cumulative [Ca2+] from 10-8 to 10-5 M. To assess the contributions of sarcoplasmic reticulum (SR) and sarcolemma voltage-gated Ca2+ channels on NE-induced contraction in arterial smooth muscle in normal rats, NE-dose response curves were measured in aortic rings (N=8) in the presence and absence of ryanodine (10 μM) and verapamil (10 μM). Forty seven percent of NE-induced contraction was due to SR Ca2+ release, which was inhibited by 10 μM ryanodine, 33% of NE-induced contraction was blocked by 10 μM verapamil, and the remaining 20% of NE-induced contraction may be due to other mechanisms such as the Na+-Ca2+ exchanger. Therefore, SR Ca2+ flux was determined by oxalate-supported Ca2+ uptake in thoracic aorta homogenates (N=8 after MI and N=12 sham). At saturating [Ca2+] required for maximal uptake ([Ca2+] = 0.9 μM), aortic SR Ca2+ uptake was increased following MI (5.3±1.5 vs. 4.0±1.1 nM Ca2+/min/mg protein, P <0.05). Conclusions: The enhanced NE-induced contraction of large arteries after MI is due to abnormal SR Ca2+ transport and it is not due to increased Ca2+-sensitivity of the contractile apparatus.

Original languageEnglish (US)
Pages (from-to)122A
JournalJournal of Investigative Medicine
Volume44
Issue number1
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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