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Published on: May 19, 2017
Effects of endothelin-1 in isolated perfused rat heart
1Medizinische Universitätsklinik, Würzburg, F.R.G.
Insights
Endothelin-1 causes significant, long-lasting coronary constriction in isolated rat hearts. This effect is amplified by inhibiting prostaglandin synthesis and reduced by ACE inhibition.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
Background:
- Endothelin-1 is a potent vasoconstrictor peptide.
- Its precise role and interactions in cardiac circulation require further elucidation.
Purpose of the Study:
- To investigate the effects of endothelin-1 on coronary flow in isolated rat hearts.
- To define interactions between endothelin-1 and other hormone systems, including sympathetic, calcium channel, prostaglandin, and ACE pathways.
Main Methods:
- Isolated isovolumic rat hearts were perfused with Krebs-Henseleit buffer.
- Endothelin-1 was administered in single boluses and cumulative doses.
- Effects were assessed in the presence of alpha- and beta-blockers, nifedipine, indomethacin, and captopril.
Main Results:
- Endothelin-1 induced a biphasic response: early vasodilation followed by irreversible late vasoconstriction.
- Coronary flow significantly decreased with increasing endothelin-1 dosage.
- Prostaglandin synthesis inhibition augmented vasoconstriction, while ACE inhibition partially antagonized it.
- Neither alpha/beta-blockers nor nifedipine altered endothelin-1 effects.
Conclusions:
- Endothelin-1 causes potent and sustained coronary constriction in isolated rat hearts.
- This effect is independent of sympathetic activity and calcium channel blockade.
- Prostaglandin synthesis inhibition enhances endothelin-1's vasoconstrictive action.
- Angiotensin-converting enzyme inhibition offers a partial counteraction to endothelin-1-induced vasoconstriction.
Abstract:
We examined the effects of the vasoconstrictor peptide endothelin-1 in the isolated heart and defined interactions of endothelin-1 with other hormone systems. Isolated isovolumic rat hearts were perfused with Krebs-Henseleit buffer at constant pressure. First, the effect of a single bolus of endothelin-1 (4-400 pmol) was followed for 90 min. The effect of high dosages (40 and 400 pmol) of endothelin-1 on coronary flow was biphasic, with an early vasodilator and a late vasoconstrictor component that was irreversible. Second, cumulative dose-response curves were obtained for endothelin-1 boluses of 0.04-400 pmol. Coronary flow declined with increasing dosages and was almost abolished at 400 pmol. Neither alpha- nor beta-blocking agents (phentolamine and propranolol) nor the Ca2(+)-channel blocker nifedipine altered the effects of endothelin-1, but prostaglandin synthesis inhibition by indomethacin significantly augmented vasoconstriction by endothelin-1. Angiotensin-converting enzyme (ACE) inhibition by captopril antagonized endothelin-1-dependent vasoconstriction to a small extent at 400 pmol. Coronary constriction due to endothelin-1 could not be reversed by nitroglycerin. We conclude that in isolated rat heart endothelin-1 causes marked and long-lasting coronary constriction. The effect is not influenced by sympathetic and Ca2(+)-channel blockade, is enhanced by prostaglandin synthesis inhibition, and is reduced by ACE inhibition.
