Pflügers Archiv - European Journal of Physiology

, Volume 432, Issue 4, pp 678–684

Negative inotropic actions of nitric oxide require high closes in rat cardiac muscle

  • Richard P. Wyeth
  • Kyosuke Temma
  • Ernst Seifen
  • Richard H. Kennedy
Original Article Heart, Circulation, Respiration and Blood; Environmental and Exercise Physiology

DOI: 10.1007/s004240050185

Cite this article as:
Wyeth, R.P., Temma, K., Seifen, E. et al. Pflügers Arch. (1996) 432: 678. doi:10.1007/s004240050185

Abstract

Initial experiments were designed to determine if vasoactive concentrations of nitric oxide (NO) alter contractility in rat heart. Contractile function was monitored in left atrial and papillary muscles (30 °C; paced at 0.5 Hz) during cumulative addition of 3-morpholino-sydnonimine-HCl(SIN-l), an agent that releases NO. At concentrations between 10−7 and 10−4 M (NO concentrations of approximately 10−8-3 × 10−7 M), SIN-1 did not affect contractility in either tissue. Similarly, 10−4 M SIN-1 did not alter the positive inotropic responses to isoproterenol or increasing extracellular [Ca+2] ([Ca+2]o). To obtain higher concentrations of NO, additional studies were conducted using authentic NO. NO-saturated stock solutions and a corresponding control solvent were adjusted to pH 1.6 with HC1. Dose-dependent effects of NO were examined by adding aliquots of the stock solutions (or control solvent) to the bathing solution. At final concentrations of 1 × 10−5- 5 × 10−4 M, NO produced transient, concentration-dependent decreases in contractility that were paralleled by reductions in buffer pH. Control solvent elicited similar reductions in pH0 and transient decreases in contractility; however, the negative inotropic action elicited by the NO-containing solution was approximately 20% greater than that observed in control conditions. These data demonstrate that only high concentrations of NO depress contractility in isolated rat cardiac muscle, and suggest that this effect is mediated by both acidosis and a pHo-independent mechanism.

Key words

Cardiac muscleContractilityExtracellular calciumIsoproterenolNitric oxidepHSIN-1

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Richard P. Wyeth
    • 1
  • Kyosuke Temma
    • 2
  • Ernst Seifen
    • 1
  • Richard H. Kennedy
    • 1
  1. 1.Department of Pharmacology & Toxicology, Mail slot 611University of Arkansas for Medical SciencesLittle RockUSA
  2. 2.Department of Veterinary PharmacologyKitasato UniversityAomoriJapan