ENDOTHELIN DILATES BOVINE PULMONARY CIRCULATION AND REVERSES HYPOXIC PULMONARY VASOCONSTRICTION

To assess the effects of endothelin 1 (ET) on the pulmonary and systemic vascular beds simultaneously, we examined the hemodynamic responses to ET in awake calves implanted with a Jarvik total artificial heart (TAH), a device that maintains constant cardiac output (CO). During basal conditions, successive incremental intravenous (i.v.) injections of 1, 3, and 10-mu-g ET caused a dose-dependent decrease in pulmonary arterial pressure (PAP), (from 24 +/- 3 to 15 +/- 1 mm Hg, p < 0.05) while having no effect on systemic arterial (SAP), left atrial (LAP), and right atrial (RAP) pressures. Administration of 30-mu-g ET i.v. also decreased PAP, had no effect on LAP and RAP, but increased SAP from 100 +/- 6 to 118 +/- 4 mm Hg (p < 0.05). The decrease in PAP was rapid, occurring within seconds and lasting 10 min, whereas the increase in SAP occurred after 2-5 min and was prolonged for greater-than-or-equal-to 20 min. As compared with injection in the right atrium, administration of 30-mu-g ET into the left atrium reduced PAP to a similar extent, but induced a greater increase in SAP (+ 32.5 +/- 4 vs + 17.5 +/- 2 mm Hg, p < 0.05). ET also dose-dependently reversed the acute pulmonary vasconstriction induced by inhalation of an hypoxic gas mixture. In all cases, pulmonary vasodilation occurred without evidence of short-term tolerance. The results demonstrate that ET is a potent in vivo pulmonary vasodilator. In calves, the predominant hemodynamic response to ET is pulmonary vasodilation, with systemic vasoconstriction apparent only at higher concentrations of the peptide.