Document Detail

Negative metabolic and coronary flow effects of decreases in cAMP and increases in cGMP in control and renal hypertensive rabbit hearts.
MedLine Citation:
PMID:  14990553     Owner:  NLM     Status:  MEDLINE    
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(-3)M), propranolol (Prop; 2 mg/kg), and Prop + 8-Br-cGMP. O(2) consumption levels (Vo(2)) in the subepicardium (Epi) and subendocardium (Endo) were determined from coronary flow (microspheres) and O(2) extraction (microspectrophotometry). Wall thickening and cAMP levels were also determined. In control, no significant change in Vo(2) was seen for the 8-Br-cGMP group, but Vo(2) was decreased from Epi (9.7 +/- 1.5 ml O(2) x min(-1) x 100 g(-1)) and Endo (10.5 +/- 0.4 ml O(2) x min(-1) x 100 g(-1)) to 6.8 +/- 0.6/7.8 +/- 0.5 ml O(2) x min(-1) x 100 g(-1) in the control Prop group. Control Prop + 8-Br-cGMP did not cause a further fall in Vo(2) but lowered Endo flow. In 1K1C, Vo(2) decreased from Epi/Endo (10.8 +/- 1.3/11 +/- 1.0 ml O(2).min(-1).100 g(-1)) to 7.8 +/- 1.1/8.7 +/- 0.5 ml O(2) x min(-1) x 100 g(-1) in the 1K1C 8-Br-cGMP group and to 7 +/- 0.5/8.1 +/- 0.5 ml O(2) x min(-1) x 100 g(-1) in the 1K1C Prop group. 1K1C Prop + 8-Br-cGMP did not cause a further fall in Vo(2) 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.
Roberto Rodriguez; Bruno Molino; Harvey R Weiss; Peter M Scholz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-02-27
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  97     ISSN:  8750-7587     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-06-28     Completed Date:  2004-12-20     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  439-45     Citation Subset:  IM    
Department of Surgery, Robert Wood Johnson Medical School, Brunswick, NJ 08903-0019, USA.
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MeSH Terms
Adrenergic beta-Antagonists / pharmacology
Blood Gas Analysis
Blood Pressure / drug effects,  physiology
Cardiac Output / drug effects,  physiology
Coronary Circulation / physiology*
Cyclic AMP / metabolism*
Cyclic GMP / analogs & derivatives*,  metabolism*,  pharmacology
Heart / physiopathology*
Heart Rate / drug effects,  physiology
Hypertension, Renovascular / metabolism*,  physiopathology*
Kidney / physiopathology
Myocardium / metabolism*
Organ Size / physiology
Oxygen Consumption / drug effects,  physiology
Propranolol / pharmacology
Second Messenger Systems / physiology
Grant Support
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 31356-94-2/8-bromocyclic GMP; 525-66-6/Propranolol; 60-92-4/Cyclic AMP; 7665-99-8/Cyclic GMP

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