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The C-terminal fragment of big endothelin-1 does not potentiate the vasoactive effects of endothelin-1
A Ottosson-Seeberger1, A Hemsén, J M Lundberg
1Department of Clinical Science, Huddinge University Hospital, Stockholm, Sweden.
Insights
The C-terminal (22-38) fragment of big endothelin-1 (big ET-1) did not significantly alter cardiovascular function in healthy humans. This study found no significant cardiovascular effects from the big ET-1 fragment infusion.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Pharmacology
Background:
- Big endothelin-1 (big ET-1) is a precursor to endothelin-1 (ET-1).
- The cardiovascular effects of the C-terminal (22-38) fragment of big ET-1 are not well understood.
- Investigating this fragment is important for understanding ET-1 related pathways.
Purpose of the Study:
- To investigate the cardiovascular effects of the C-terminal (22-38) fragment of big ET-1 in healthy humans.
- To determine if the (22-38) fragment modifies the cardiovascular actions of ET-1.
Main Methods:
- Intravenous infusion of the (22-38) fragment at varying doses in 10 healthy subjects.
- Control group received saline infusion.
- ET-1 infusion alone or combined with the (22-38) fragment in two subjects.
Main Results:
- The (22-38) fragment infusion did not alter heart rate, mean arterial blood pressure, cardiac output, or vascular resistance.
- A slight fall in renal blood flow was observed, similar to control studies.
- Pulmonary pressures (MPAP, PCWP) decreased post-infusion but did not differ from saline controls.
- The fragment did not modify ET-1's cardiovascular effects.
Conclusions:
- The exogenous C-terminal (22-38) fragment of big ET-1 does not appear to cause significant cardiovascular effects in healthy humans.
- The fragment does not antagonize or potentiate the cardiovascular effects of ET-1.
Abstract:
The aim was to study the cardiovascular effects of the C-terminal (22-38) fragment of big endothelin-1, which is produced by the cleavage of big endothelin-1 (big ET-1) to endothelin-1 (ET-1). An intravenous infusion of the (22-38) fragment (4, 8 and 12 pmol kg-1 min-1, each dose for 10 min) was given to 10 healthy subjects. Four control subjects received 0.9% saline. Two additional subjects received ET-1 1 (0.2 and 4 pmol kg-1 min-1, each dose for 20 min) alone or combined with an equimolar infusion of the (22-38) fragment on two separate occasions. The fragment infusion did not alter heart rate, mean arterial blood pressure, cardiac output, systemic or pulmonary vascular resistance, splanchnic, cerebral or forearm blood flow. Renal blood flow showed a slight fall (11%, P < 0.001) in the fragment group of the same magnitude as in a previous control study. After the fragment infusion, a decrease in mean pulmonary arterial pressure (MPAP) by 12% (P < 0.01) and in pulmonary capillary wedge pressure (PCWP) by 31% (P < 0.001) was noted, which did not differ from the pulmonary pressures in the saline-infused control group. The (22-38) fragment, when combined with ET-1, was not able to modify the effects of ET-1 on heart rate, mean arterial blood pressure, splanchnic and renal blood flow. Consequently, the exogenous (22-38) fragment does not seem to cause any significant cardiovascular effects in healthy humans.