-The endothelin (ET) system is involved in the regulation of myocardial function in health as well as in several diseases, such as congestive heart failure, myocardial infarction, and septic myocardial depression. Conflicting results have been reported regarding the acute contractile properties of ET-1. We therefore investigated the effects of intracoronary infusions of ET-1 and of the selective ETB receptor-selective agonist sarafotoxin 6c with increasing doses in anesthetized pigs. Myocardial effects were measured through analysis of the left ventricular pressure-volume relationship. ET-1 elicited increases in the myocardial contractile status (end-systolic elastance value of 0.94 Ϯ 0.11 to 1.48 Ϯ 0.23 and preload recruitable stroke work value of 68.7 Ϯ 4.7 to 83.4 Ϯ 7.2) that appear to be mediated through ETA receptors, whereas impairment in left ventricular isovolumic relaxation ( ϭ 41.5 Ϯ 1.4 to 58.1 Ϯ 5.0 and t1/2 ϭ 23.0 Ϯ 0.7 to 30.9 Ϯ 2.6, where is the time constant for pressure decay and t1/2 is the half-time for pressure decay) was ETB receptor dependent. In addition, intravenous administration of ET-1 impaired ventricular relaxation but had no effect on contractility. Intracoronary sarafotoxin 6c administration caused impairments in left ventricular relaxation ( from 43.3 Ϯ 1.8 to 54.4 Ϯ 3.4) as well as coronary vasoconstriction. In conclusion, ET-1 elicits positive inotropic and negative lusitropic myocardial effects in a pig model, possibly resulting from ETA and ETB receptor activation, respectively. cardiac; inotropy; end-systolic elastance; diastolic; porcine; sarafotoxin THE ENDOTHELINS ARE A FAMILY of 21 amino acid peptides with powerful vasoactive properties, which were first described in 1988 (48). Endothelin-1 (ET-1), which is probably the most important of the endothelins as far as effects in humans are concerned, is mainly produced by the vascular endothelium. This vasoconstrictive peptide acts on two groups of receptors: ET A and ET B receptors, located on vascular smooth muscle cells mediating contraction, and ET B receptors, located on the endothelium mediating vasodilation by release of nitric oxide and prostacyclin (1, 10, 31). In the heart, the predominant ET isopeptide is ET-1 (30), and both ET A and ET B receptor mRNA are found in atrial and ventricular myocardium, the conducting system, and endocardial cells as well as in coronary arteries (3,26). The ET system and ET-1 binding properties on cardiomyocytes are largely similar in pigs and humans (25).The ET system is involved in the cardiovascular response to several disease processes. Increased plasma levels of ET-1 have been noted in association with acute myocardial infarction, congestive heart failure, pulmonary hypertension, and septic shock (44). There are numerous reports regarding the cardiac effects of ET-1. The majority of studies done in larger animals or humans seems to indicate positive inotropic effects of ET-1 under nondisease conditions. Several studies have been performed in vitro in various species with conflictin...