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Background: The vasoconstrictor action of endothelin-1 (ET-1) is mediated through ET A and ET B receptor subtypes on vascular smooth muscle. ET B receptors are also present on the vascular endothelium where they mediate vasodilation. Animal studies suggest that the ET B receptor also acts as a clearance receptor for endothelin. Aims: To investigate the effects of a selective ET A and a selective ET B receptor antagonist alone and in combination on haemodynamics and circulating concentrations of ET-1 in patients with chronic heart failure. Results: Infusion of BQ-123 (n=10), a selective ET A receptor antagonist, led to systemic vasodilation and did not change plasma ET-1 concentrations (1.38F0.82 to 1.38F0.91 fmol/ml, ns). Infusion of BQ-788 (n=8) led to systemic vasoconstriction with a rise in plasma ET-1 (1.84F1.06 to 2.73F0.99 fmol/ml, pb0.01). The addition of BQ-123 to BQ-788 led to systemic and pulmonary vasodilation with no further increase in plasma ET-1 concentrations (2.80F1.14 to 2.90F1.20 fmol/ml, ns). Conclusion: The rise in plasma ET-1 concentrations in response to selective blockade of ET B receptors and the associated adverse haemodynamic effects suggest that ET B receptors have a role in the clearance of ET-1 in man and that their blockade may not be advantageous for patients with heart failure.

Twenty-two male and female patients who had recently suffered a myocardial infarction were randomly assigned to a treatment group who participated in a 10-week exercise-based cardiac rehabilitation programme or a routine care group who did not participate in the rehabilitation programme. Physiological and psychological function were assessed before the programme started and after it finished. Results indicated that the treatment group did not improve physiological functioning more than the control group but they did evidence statistically significant improved psychological functioning. This investigation appears to be the first attempt to assess the potential benefits of an exercise-based cardiac rehabilitation programme in Glasgow and supports the suggestion that exercise-based cardiac rehabilitation has psychological benefits.

Exogenous ET-1, when infused to achieve plasma concentrations similar to those in severe heart failure and pulmonary hypertension, causes systemic but not pulmonary vasoconstriction.