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Effects of N-dimethyl propranolol (UM-272) on isolated cardiac mitochondria and microsomes
Abstract:
N-dimethyl propranolol (UM-272) has been shown to protect the heart from injury produced by ischemia. In the present study we examined the effects of UM-272 on the function of isolated rabbit cardiac mitochondria and microsomes. Concentrations of 13 micrometers or below were without effect on these organelles. UM-272 (130 micrometers) significantly decreased respiratory control of mitochondria utilizing glutamate plus malate, or succinate, as substrates. At 1.3 mM, UM-272 increased the initial rate of basal oxygen consumption, and decreased the rate of ADP-stimulated respiration. UM-272 was slightly more potent than d,1-propranolol. At a concentration of 1.3 mM, UM-272 significantly decreased the rate and maximum amount of 45CaCl2 accumulated by microsomes in the presence of ATP and oxalate. Concentrations of drug that suppress cellular metabolism are close to those required to prevent ischemic injury. We suggest that sarcolemmal and intracellular actions of the drug which help to depress oxygen demand and ATP utilization may account for part of the drug's protective effects.
Insights
N-dimethyl propranolol (UM-272) protects the heart by impacting cellular energy use. This drug affects cardiac mitochondria and microsomes, potentially reducing oxygen demand and ATP utilization to prevent ischemic injury.
Area of Science:
- Cardiovascular Pharmacology
- Mitochondrial Function
- Cellular Metabolism
Background:
- N-dimethyl propranolol (UM-272) demonstrates cardioprotective effects against ischemic injury.
- Understanding the precise mechanisms of UM-272's protective action is crucial.
Purpose of the Study:
- To investigate the effects of UM-272 on isolated rabbit cardiac mitochondria and microsomes.
- To determine the concentrations at which UM-272 impacts organelle function.
Main Methods:
- Isolated rabbit cardiac mitochondria and microsomes were utilized.
- Oxygen consumption, respiratory control, and calcium uptake were measured.
- Effects of varying UM-272 concentrations were assessed.
Main Results:
- UM-272 at 130 micrometers significantly impaired mitochondrial respiratory control.
- At 1.3 mM, UM-272 altered basal and ADP-stimulated mitochondrial respiration.
- UM-272 (1.3 mM) reduced calcium accumulation in cardiac microsomes.
Conclusions:
- UM-272 affects cardiac mitochondrial and microsomal function at higher concentrations.
- The drug's ability to depress cellular oxygen demand and ATP utilization may contribute to its cardioprotective effects.
- UM-272 exhibits slightly greater potency than d,l-propranolol in these assays.