Abstract
Experiments were conducted to determine the ability of the newly discovered ETA receptor antagonist, BQ-123, to inhibit the pressor responses to several members of the human endothelin peptide family in anesthetized rats. Big ET-1 produced a greater increase in mean arterial pressure compared to ET-1 (67 ± 10% vs. 44 ± 4%, p < 0.05; both at 1 nmol/kg i.v.). Prior administration of BQ-123 (10 mg/kg i.v.) was more effective at inhibiting the response to Big ET-1 compared to ET-1. Following ETA receptor blockade, ET-1 produced a small, but significant, increase in mean arterial pressure (15 ± 2%) while Big ET-1 had no effect (5 ± 2%). Big ET-3 and ET-3 at 1 nmol/kg i.v. produced similar increases in mean arterial pressure, although less than that produced by either Big ET-1 or ET-1 (p < 0.05). ETA receptor antagonism blocked 64% of the pressor response to both Big ET-3 and ET-3. We conclude that blockade of pressor responses to each of the endothelin peptides suggests that the increases in arterial pressure ...
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