Effect of cyclic GMP on oxygen consumption is attenuated in renal hypertensive-induced hypertrophic cardiac myocytes

We tested the hypothesis that cardiac myocytes from renal hypertensive (1 kidney 1 clip - 1K1C) cardiac hypertrophied rabbits require higher cyclic GMP levels to similarly lower O₂ consumption (VO₂) when compared with controls, because of differences in guanylate cyclase (GC). Using isolated cardiac myocytes from control and 1K1C New Zealand white rabbits, VO₂ (nl/min/10⁴ cells), GC activity (pmol/mg protein/min), and cGMP levels (fmol/104 cells) were obtained after stimulation of GC with increasing doses of nitroprusside (NP), carbon monoxide (CO), or guanylin (10^-8 to 10^-5 M). Basal VO₂ in 1K1C vs. control myocytes was comparable (307±21 vs. 299±22). VO₂was similarly decreased when GC was stimulated in 1K1C vs. control using NP (203±30 vs. 210±17), CO (I40±14 vs. 153±13), and guanylin (158±22 vs. 157±8). GC activity in 1K1C vs. control was not statistically different in basal (2.2±0.5 vs. 3.7±0.8) or stimulated (110±27 vs. 99.318.8) conditions. Basal cGMP was markedly elevated in 1K1C vs. control (176±28 vs. 85±13) myocytes, and greater increases in cGMP were noted in 1K1C vs. controls after stimulation by NP (408±59 vs. 216±60), CO (281±36 vs. 184±46), and guanylin (263±25 vs. 165±26). The 1K1C hypertrophic myocytes require higher levels of intracellular cGMP than controls to produce the same decrement in VO₂, indicating an attenuated response to cGMP. This effect is not caused by differences in guanylate cyclase activity.