title: Effects of the nitric oxide donor sodium nitroprusside on intracellular pH and contraction in hypertrophied myocytes.
abstract: BACKGROUND
  We compared the effects of the nitric oxide donor sodium nitroprusside (SNP) on intracellular pH (pHi), intracellular calcium concentration ([Ca2+]i) transients, and cell contraction in hypertrophied adult ventricular myocytes from aortic-banded rats and age-matched controls.
  
  
  RESULTS
  pHi was measured in individual myocytes with SNARF-1, and [Ca2+]i transients were measured with indo 1 simultaneously with cell motion. Experiments were performed at 37 degrees C in myocytes paced at 0.5 Hz in HEPES-buffered solution (extracellular pH = 7.40). At baseline, calibrated pHi, diastolic and systolic [Ca2+]i values, and the amplitude of cell contraction were similar in hypertrophied and control myocytes. Exposure of the control myocytes to 10(-6) mol/L SNP caused a decrease in the amplitude of cell contraction (72 +/- 7% of baseline, P < .05) that was associated with a decrease in pHi (-0.10 +/- 0.03 U, P < .05) with no change in peak systolic [Ca2+]i. In contrast, in the hypertrophied myocytes exposure to SNP did not decrease the amplitude of cell contraction or cause intracellular acidification (-0.01 +/- 0.01 U, NS). The cGMP analogue 8-bromo-cGMP depressed cell shortening and pHi in the control myocytes but failed to modify cell contraction or pHi in the hypertrophied cells. To examine the effects of SNP on Na(+)-H+ exchange during recovery from intracellular acidosis, cells were exposed to a pulse and washout of NH4Cl. SNP significantly depressed the rate of recovery from intracellular acidosis in the control cells compared with the rate in hypertrophied cells.
  
  
  CONCLUSIONS
  SNP and 8-bromo-cGMP cause a negative inotropic effect and depress the rate of recovery from intracellular acidification that is mediated by Na(+)-H+ exchange in normal adult rat myocytes. In contrast, SNP and 8-bromo-cGMP do not modify cell contraction or pHi in hypertrophied myocytes.
authors.affiliation: Charles A. Dana Research Institute, Harvard-Thorndike Laboratory, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: N
authors.initials: N
authors.lastname: Ito
authors.forename: J
authors.initials: J
authors.lastname: Bartunek
authors.forename: K W
authors.initials: KW
authors.lastname: Spitzer
authors.forename: B H
authors.initials: BH
authors.lastname: Lorell
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D006859:Hydrogen; D006152:Cyclic GMP