CGMP level that reduces cardiac myocyte O2consumption is altered in renal hypertension

Abstract

We tested the hypothesis that cardiac myocytes from hypertensive (one kidney, one clip; 1K,1C) cardiac-hypertrophied rabbits require higher guanosine 3',5'-cyclic monophosphate (cGMP) to similarly lower O2 consumption than control myocytes and that this effect is caused by differences in guanylate cyclase activity. Using isolated myocytes from control and 1K,1C New Zealand White rabbits, we obtained O2 consumption (nl O2 x min(-1) x 10(5) cells) and cGMP (fmol/10(5) cells) levels after stimulation of guanylate cyclase with nitroprusside, CO, or guanylin (10(-8)-10(-5) M). Soluble guanylate cyclase activity was also determined. Basal cGMP was elevated in 1K,1C vs. control (176 +/- 28 vs. 85 +/- 13) myocytes. cGMP increased in 1K,1C and control myocytes after stimulation with nitroprusside, CO, and guanylin. Guanylate cyclase activity in 1K,1C vs. control myocytes was not statistically different. Basal O2 consumption in 1K,1C vs. control myocytes was comparable (307 +/- 1 vs. 299 +/- 22). O2 consumption was similarly decreased when guanylate cyclase was stimulated. Control regression equations correlating cGMP and O2 consumption were O2 consumption = -1.46 x [cGMP] + 444.65 (r = 0.96) for CO, O2 consumption = -0.58 x [cGMP] + 328.48 (r = 0.82) for nitroprusside, and O2 consumption = -1.25 x [cGMP] + 389.15 (r = 0.88) for guanylin. The 1K,1C regression equations were O2 consumption = -1.36 x [cGMP] + 537.81 (r = 0.97) for CO, O2 consumption = -0.23 x [cGMP] + 307.30 (r = 0.88) for nitroprusside, and O2 consumption = -1.27 x [cGMP] + 502.91 (r = 0.89) for guanylin. These data indicate that 1K,1C hypertrophic myocytes had higher cGMP than controls at every level of O2 consumption. This effect was not caused by differences in basal or maximal guanylate cyclase activity.