EFFECTS OF THE NITRIC-OXIDE DONOR SODIUM-NITROPRUSSIDE ON INTRACELLULAR PH AND CONTRACTION IN HYPERTROPHIED MYOCYTES

Background We compared the effects of the nitric oxide donor sodium ni troprusside (SNP) on intracellular pH (pH(i)), intracellular calcium c oncentration ([Ca2+](i)) transients, and cell contraction in hypertrop hied adult ventricular myocytes from aortic-banded rats and age-matche d controls. Methods and Results pH(i) was measured in individual myocy tes with SNARF-1, and [Ca2+](i) transients were measured with indo 1 s imultaneously with cell motion. Experiments were performed at 37 degre es C in myocytes paced at 0.5 Hz in HEPES-buffered solution (extracell ular pH=7.40). At baseline, calibrated pH(i), 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 contrac tion (72+/-7% of baseline, P<.05) that was associated with a decrease in pH(i) (-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 n ot decrease the amplitude of cell contraction or cause intracellular a cidification (-0.01+/-0.01 U, NS). The cGMP analogue 8-bromo-cGMP depr essed cell shortening and pH(i) in the control myocytes but failed to modify cell contraction or pH(i) in the hypertrophied cells. To examin e the effects of SNP on Na+-H+ exchange during recovery from intracell ular acidosis, cells were exposed to a pulse and washout of NH4Cl. SNP significantly depressed the rate of recovery from intracellular acido sis in the control cells compared with the rate in hypertrophied cells . Conclusions SNP and 8-bromo-cGMP cause a negative inotropic effect a nd depress the rate of recovery from intracellular acidification that is mediated by Na+-H+ exchange in normal adult rat myocytes. In contra st, SNP and 8-bromo-cGMP do not modify cell contraction or pH(i) in hy pertrophied myocytes.