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Long-lasting treatment with adenosine receptor antagonists: effects on hypoxic tolerance and vascular responsiveness
A Cseppentö1, A Ujfalusi, K Antal
1Department of Pharmacology, University Medical School of Debrecen, Hungary.
Abstract:
In electrically driven myocardial preparations obtained from chronically methylxanthine-[aminophylline (APH) and 8-phenyltheophylline (8-PT)] or solvent(DMSO)-treated guinea pigs no differences were found in alteration of mechanical activity under hypoxia and reoxygenation. The vasoconstrictor effects observed after in vitro exposure of pulmonary arterial preparations (excised from either methylxanthine- or solvent-treated guinea pigs) to both noradrenaline and PGF2 alpha were also similar. In methylxanthine-treated vascular tissues, however, nitroglycerin and NO exerted more pronounced vasorelaxant effect than in specimens prepared from solvent-treated guinea pigs.
Insights
Methylxanthines like aminophylline did not alter myocardial mechanical activity during hypoxia. However, these compounds enhanced vasorelaxant responses to nitroglycerin and nitric oxide in vascular tissues.
Area of Science:
- Pharmacology and Cardiovascular Physiology
- Investigating the effects of methylxanthines on cardiovascular function.
Background:
- Methylxanthines, including aminophylline (APH) and 8-phenyltheophylline (8-PT), are known to affect cardiovascular function.
- Understanding their impact on myocardial and vascular tissue responses is crucial for therapeutic applications.
Purpose of the Study:
- To investigate the effects of chronic methylxanthine treatment on guinea pig myocardial and pulmonary arterial preparations.
- To compare the mechanical activity of myocardial tissue and the vasoconstrictor/vasorelaxant responses of vascular tissue from methylxanthine-treated and control animals.
Main Methods:
- Electrically driven myocardial preparations from guinea pigs chronically treated with methylxanthines (APH, 8-PT) or solvent (DMSO) were studied.
- Pulmonary arterial preparations were exposed to vasoconstrictors (noradrenaline, PGF2 alpha) and vasorelaxants (nitroglycerin, NO).
- Mechanical activity and contractile/relaxant responses were measured and compared between groups.
Main Results:
- No significant differences were observed in the mechanical activity of myocardial preparations under hypoxia and reoxygenation between methylxanthine- and solvent-treated groups.
- Vasoconstrictor responses to noradrenaline and PGF2 alpha in pulmonary arterial preparations were similar in both treatment groups.
- Methylxanthine-treated vascular tissues exhibited significantly more pronounced vasorelaxant effects from nitroglycerin and nitric oxide compared to solvent-treated tissues.
Conclusions:
- Chronic methylxanthine administration does not alter myocardial mechanical function during hypoxic stress.
- While not affecting vasoconstriction, methylxanthines potentiate the vasorelaxant effects of nitroglycerin and nitric oxide in pulmonary arteries.
- These findings suggest a specific enhancement of NO-mediated or nitroglycerin-induced vasodilation by methylxanthines.