Hemodynamic effect of human and rat endothelin administration into conscious rats

Abstract

The hemodynamic effect of human-porcine endothelin (endothelin-1, ET-1) and rat endothelin (endothelin-3, ET-3) administration into conscious male, Sprague-Dawley rats was investigated. Bolus administration of ET-1 produced sustained, dose-dependent increases in mean arterial pressure (MAP) and total peripheral resistance (TPR). ET-1 also produced dose-dependent decreases in cardiac output (CO) and heart rate (HR), although dose-dependent changes in stroke volume (SV) were not observed. Similar results were obtained with 1-h infusions of ET-1. Infusions of ET-1 produced dose-dependent elevations in MAP that were sustained throughout the infusion period and for 1 h thereafter. TPR, CO, and HR were significantly altered only by the highest infusion rate of ET-1, whereas SV was not significantly affected by any rat of infusion of the peptide. These data indicate that ET-1 produces an overall dose-dependent increase in MAP through a mechanism involving an unusually prolonged increase in TPR. Similar experiments using ET-3 indicate that this sequence, acting through a mechanism similar to that of ET-1, may be metabolized more quickly, since the duration of its blood pressure effect is shorter than that of ET-1. Furthermore, in contrast to ET-1, ET-3 did not decrease HR and CO. The two peptide sequences do, however, appear to be equally efficacious as pressor agents, since the maximal change in MAP and time of onset of the maximal change in MAP and time of onset of the maximal change in MAP induced by either peptide sequence are statistically comparable. Factors effecting endogenous release or synthesis of the peptide could cause changes in systemic hemodynamics similar to those observed in essential hypertension.