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J Appl Physiol 97: 439-445, 2004. First published February 27, 2004; doi:10.1152/japplphysiol.01115.2003
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HIGHLIGHTED TOPICS
Skeletal and Cardiac Muscle Blood Flow

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

Roberto Rodriguez,1 Bruno Molino,1 Harvey R. Weiss,2 and Peter M. Scholz1

Departments of 1Surgery and 2Physiology & Biophysics, Heart and Brain Circulation Laboratory, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854-5635

Submitted 15 October 2003 ; accepted in final form 16 December 2003

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 (O2) 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 O2 was seen for the 8-Br-cGMP group, but O2 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 O2 but lowered Endo flow. In 1K1C, O2 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 O2 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.

myocardial oxygen consumption; second messengers; coronary blood flow; hypertension


Address for reprint requests and other correspondence: P. M. Scholz, Dept. of Surgery, UMDNJ-Robert Wood Johnson Medical School, One Robert Wood Johnson Place, CN-19, New Brunswick, NJ 08903-0019 (E-mail: scholz{at}umdnj.edu).






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