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Removal of endothelial function in coronary resistance vessels by saponin
1Department of Biological Research, Dr. Karl Thomae GmbH, Biberach, FRG.
Insights
Saponin treatment specifically damages the endothelium in guinea pig coronary resistance vessels. This damage blocks endothelium-derived relaxing factors, altering vessel responses to various vasoactive substances.
Area of Science:
- Cardiovascular Physiology
- Endothelial Biology
- Vascular Pharmacology
Background:
- Endothelium-derived relaxing factor (EDRF) mediated effects are key in coronary resistance vessels.
- Endothelium removal is typically limited to larger vessels, hindering studies on resistance vessels.
- Investigating direct endothelial damage is crucial for understanding its role in coronary circulation.
Purpose of the Study:
- To investigate the effect of specific endothelial damage using saponin on coronary resistance vessels.
- To determine how saponin-induced endothelial damage alters responses to vasoactive agents.
- To differentiate the role of the endothelium from vascular smooth muscle in regulating coronary tone.
Main Methods:
- Isolated perfused guinea pig heart model.
- Infusion of saponin solution (50 µg/ml) to selectively damage endothelium.
- Assessment of coronary flow changes in response to carbachol, histamine, serotonin, angiotensin I, angiotensin II, and sodium nitroprusside.
- Electron microscopy to confirm endothelial damage and vascular smooth muscle integrity.
- Comparison with gossypol inhibition of endothelium-derived relaxing factor.
Main Results:
- Saponin treatment completely blocked and reversed vasodilation to carbachol, histamine, and serotonin.
- Vasoconstriction to angiotensin I was attenuated, while angiotensin II effects remained unchanged.
- Vasodilatory response to sodium nitroprusside was unaffected, indicating preserved smooth muscle function.
- Gossypol inhibited carbachol-induced vasodilation but did not cause vasoconstriction.
- Electron microscopy confirmed endothelium destruction with intact vascular smooth muscle.
Conclusions:
- The vascular endothelium exerts a significant regulatory influence on coronary resistance vessels.
- Saponin effectively eliminates this endothelial regulation, providing a model for studying its absence.
- Endothelium-derived relaxing factors play a critical role in mediating vasodilation in response to specific stimuli.
- Coronary resistance vessel function is dependent on an intact endothelium for proper vasodilation and tone regulation.
Abstract:
Studies of the role of the endothelium in coronary resistance vessels are limited to investigations of endothelium-derived relaxing factor mediated effects using various blocking agents. Endothelium removal as an alternative approach, is restricted to larger epicardial vessels. This study demonstrates the effect of endothelial damage by saponin on coronary resistance vessels remaining intact within the heart. In an isolated perfused guinea pig heart a saponin-containing solution (50 micrograms/ml) was infused over 2 min to damage specifically the endothelium. Increases of coronary flow in response to carbachol, histamine, and serotonin were completely blocked and reversed to decreases. Angiotensin-I-induced vasoconstriction was attenuated, whereas angiotensin-II-induced vasoconstriction remained unchanged. Vasodilatory response to sodium-nitroprusside was not attenuated by saponin-treatment. In contrast inhibition of endothelium derived relaxing factor by gossypol inhibited carbachol-induced vasodilation but did not result in vasoconstriction. Electron microscopic examination ensured that while the endothelium was destroyed by saponin-treatment the vascular smooth muscle was left intact. Our data indicate a regulating influence of the vascular endothelium on coronary resistance vessels which can be totally eliminated by saponin-treatment.