cGMP level that reduces cardiac myocyte O-2 consumption is altered in renal hypertension

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 O-2 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 O-2 consumption (nl O-2.min(-1).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 O-2 consumption in 1K,1C vs. control myocytes was comparable (307 +/- 1 vs. 299 +/- 22). O-2 consumption was similarly decreased when guanylate cyclase was stimulated. Control regression equations correlating cGMP and O-2 consumption were O-2 consumption = -1.46.[cGMP] + 444.65 (r = 0.96) for CO, O-2 consumption = -0.58.[cGMP] + 328.48 (r = 0.82) for nitroprusside, and O-2 consumption = -1.25 [cGMP] + 389.15 (r = 0.88) for guanylin. The 1K,1C regression equations were O-2 consumption = -1.36.[cGMP] + 537.81(r = 0.97) for CO, O-2 consumption = -0.23.[cGMP] + 307.30 (r = 0.88) for nitroprusside, and O-2 consumption = -1.27.[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 O-2 consumption. This effect was not caused by differences in basal or maximal guanylate cyclase activity.