Submitted on October 15, 2003
Accepted on December 16, 2003
Negative Metabolic and Coronary Flow Effects of Decreases in cAMP and Increases in cGMP in Control and Renal Hypertensive Rabbit Hearts
Roberto Rodriguez1, Bruno Molino1, Harvey R Weiss2, and Peter M Scholz1*
1 Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
2 Physiology&Biophysics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ, USA
* To whom correspondence should be addressed. E-mail: scholz{at}umdnj.edu.
The interaction during stimulation of cGMP and inhibition of cAMP was investigated in control and renal hypertensive hearts. Control and hypertensive (one kidney, one clip, 1K1C) rabbits were used. The anesthetized open-chest groups were: vehicle, 8-bromo-cGMP (8-Br-cGMP, 10-3M), propranolol (Prop, 2mg/kg), propranolol+8-bromo-cGMP (8-Br-cGMP+Prop). Oxygen consumption (VO2) in the subepicardium (EPI) and subendocardium (ENDO) was 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/100g)/ENDO (10.5±0.4), to (6.8±0.6/7.8±0.5) in the control Prop group. Control 8-Br-cGMP+Prop did not cause a further fall in VO2, but lowered ENDO flow. In 1K1C, VO2 decreased from EPI (10.8±1.3 ml O2/min/100g)/ENDO (11±1.0), to (7.8±1.1/8.7±0.5) in the 1K1C 8-Br-cGMP group and to (7±0.5/8.1±0.5) in the 1K1C Prop group. 1K1C 8-Br-cGMP+Prop did not cause a further fall in VO2, but lowered blood flow. No significant changes in cAMP level were present with 8-Br-cGMP in control or 1K1C, but significant decreases were seen with Prop in both control and 1K1C. No further change was seen in 8-Br-cGMP+Prop 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 non-additive.
