Negative metabolic and coronary flow effects of decreases in cAMP and increases in cGMP in control and renal hypertensive rabbit hearts

Abstract

The interaction during stimulation of cGMP and inhibition of cAMP was investigated in control and renal hypertensive hearts. Control and hypertensive [1 kidney, 1 clip (1K1C)] rabbits were used. The anesthetized open-chest groups were vehicle, 8-bromo-cGMP (8-Br-cGMP; 10−3M), propranolol (Prop; 2 mg/kg), and Prop + 8-Br-cGMP. O2 consumption levels (V̇o2) in the subepicardium (Epi) and subendocardium (Endo) were determined from coronary flow (microspheres) and O2 extraction (microspectrophotometry). Wall thickening and cAMP levels were also determined. In control, no significant change in V̇o2 was seen for the 8-Br-cGMP group, but V̇o2 was decreased from Epi (9.7 ± 1.5 ml O2·min−1·100 g−1) and Endo (10.5 ± 0.4 ml O2·min−1·100 g−1) to 6.8 ± 0.6/7.8 ± 0.5 ml O2·min−1·100 g−1 in the control Prop group. Control Prop + 8-Br-cGMP did not cause a further fall in V̇o2 but lowered Endo flow. In 1K1C, V̇o2 decreased from Epi/Endo (10.8 ± 1.3/11 ± 1.0 ml O2·min−1·100 g−1) to 7.8 ± 1.1/8.7 ± 0.5 ml O2·min−1·100 g−1 in the 1K1C 8-Br-cGMP group and to 7 ± 0.5/8.1 ± 0.5 ml O2·min−1·100 g−1 in the 1K1C Prop group. 1K1C Prop + 8-Br-cGMP did not cause a further fall in V̇o2 but lowered blood flow. No significant changes in cAMP levels were present with 8-Br-cGMP in control or 1K1C rabbits, but significant decreases were seen with Prop in both control and 1K1C rabbits. No further change was seen in Prop + 8-Br-cGMP for either control or 1K1C. Thus the negative metabolic effect of stimulating cGMP was seen only in the hypertensive rabbit heart. The negative metabolic effect of inhibiting cAMP was seen in both the control and the hypertensive rabbit heart. However, the negative metabolic effects of cGMP and cAMP were nonadditive.