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

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 (Vo2) 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 Vo2 was seen for the 8-Br-cGMP group, but Vo2 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 Vo2 but lowered Endo flow. In 1K1C, Vo2 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...