Related Experiment Videos
cGMP level that reduces cardiac myocyte O2 consumption is altered in renal hypertension
1Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635, USA.
Insights
Cardiac myocytes from hypertensive rabbits have higher guanosine 3
Area of Science:
- Cardiovascular Physiology
- Cellular Biology
Background:
- Hypertension leads to cardiac hypertrophy, altering myocyte function.
- Guanylate cyclase (GC) and cyclic guanosine monophosphate (cGMP) signaling are crucial in regulating cardiac function.
- Understanding cGMP's role in hypertrophied myocytes is key to addressing cardiac dysfunction.
Purpose of the Study:
- To test if cardiac myocytes from hypertensive rabbits require higher cGMP levels to decrease oxygen consumption compared to control myocytes.
- To determine if differences in guanylate cyclase activity explain these effects.
Main Methods:
- Isolated cardiac myocytes from control and one kidney, one clip (1K,1C) hypertensive rabbits were used.
- Oxygen consumption and cGMP levels were measured after stimulating GC with nitroprusside, CO, or guanylin.
- Soluble guanylate cyclase activity was assessed.
Main Results:
- Basal cGMP levels were significantly higher in 1K,1C myocytes compared to controls.
- Stimulation with various agents increased cGMP in both groups, but 1K,1C myocytes maintained higher cGMP levels across all oxygen consumption rates.
- Guanylate cyclase activity did not differ significantly between 1K,1C and control myocytes.
- Oxygen consumption decreased similarly in both groups upon GC stimulation.
Conclusions:
- Cardiac myocytes from hypertensive, hypertrophied rabbits exhibit elevated cGMP levels independent of guanylate cyclase activity.
- The observed higher cGMP in hypertrophic myocytes does not stem from altered basal or maximal GC activity.
- These findings suggest a complex regulation of cGMP in cardiac hypertrophy affecting cellular energetics.
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.