NEGATIVE METABOLIC EFFECTS OF CYCLIC-GMP IN QUIESCENT CARDIOMYOCYTES ARE NOT RELATED TO L-TYPE CALCIUM-CHANNEL ACTIVITY

We tested the hypothesis that the negative metabolic effects of elevat ing cyclic CMP act through inhibition of L-type calcium channels in qu iescent cardiac myocytes. The steady state O-2 consumption (VO2) of ve ntricular myocytes, isolated from hearts of New Zealand white rabbits, was measured in a glass chamber using Clark-type oxygen electrodes. T he cellular cyclic GMP levels were determined by radioimmunoassay at b aseline with either 0.5 mM or 2.0 mM of Ca2+, sodium nitroprusside at increasing concentration (10(-8,-6,-4) M) with and without pretreatmen t by BAY K8644 10(-5) M (L-type Ca2+ channel activator) in 0.5 mM Ca2, or nitroprusside with and without pretreatment with nifedipine 10(-4 ) M (L type Ca2+ channel blocker) in 2.0 mM Ca2+. In the 0.5 mM. Ca2medium, basal VO2 was 459 +/- 104 (nl O-2/min per 10(5) myocytes) with a corresponding cyclic GMP level of 112 +/- 23 (fmol/10(5) myocytes). With nitroprusside 10(-4) M, VO2 was decreased to 285 +/- 39 and cycl ic GMP level was significantly elevated to 425 +/- 128. In the same me dium, VO2 was slightly increased by BAY K8644 10(-5) M while the cycli c GMP level did not change. With BAY K8644 10(-5) M, nitroprusside 10( -4) M decreased VO2 and increased cyclic GMP to a level which was simi lar to cells treated with nitroprusside alone. In the 2.0 mM Ca2+ medi um, the basal VO2 and cyclic GMP were 518 +/- 121 and 137 +/- 24. In t he presence of nitroprusside 10(-4) M, VO2 was decreased to 285 +/- 39 and cyclic GMP was increased to 454 +/- 116. In the same medium, nife dipine 10(-4) M significantly decreased VO2, while the cyclic GMP leve l was comparable to the baseline. After nifedipine 10(-4) M, nitroprus side 10(-4) M decreased VO2 and increased cyclic GMP to levels which w ere similar to control. Therefore, in quiescent cardiac myocytes, the negative metabolic effects associated with cyclic GMP were not primari ly mediated through inhibition of L-type Ca2+ channels.