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1 There are at least two subtypes of vascular endothelin (ET) receptors. Stimulation of the ETA receptors on vascular smooth muscle cells leads to vasoconstriction, whereas activation of the ETB receptors on endothelial cells elicits vasodilatation. Several reports in the literature have suggested the presence of a vasoconstrictor non-ETA receptor on vascular smooth muscle which has pharmacological similarities to the ETB receptor. The present study was undertaken to determine the location of this ETB-like receptor within the vascular system. 2 Fourteen vascular smooth muscle preparations from six species were used to determine the effect of the ETA receptor antagonist, BQ-123, on concentration-response curves elicited by ET-1 and the ability of the ETB receptor agonist, sarafotoxin S6c, to cause contraction. The vessels fell into two categories. One group was sensitive to BQ-123 and insensitive to sarafotoxin S6c and, thus, probably contained ETA receptors. The other group, with vasoconstrictor ETB-like receptors, was insensitive to BQ-123 and sensitive to sarafotoxin S6c. 3 Vessels from cynomolgus monkeys, when studied in vitro, appeared to contain primarily ETA receptors, although the potency of BQ-123 was quite variable, suggesting the possibility of ETA receptor subtypes. In contrast, both ET-1 and sarafotoxin S6c, given as intravenous injections in conscious monkeys, produced transient, equipotent, and dose-related increases in blood pressure. The highest dose of sarafotoxin S6c (1 nmol kg-', i.v.) also caused a marked secondary depressor response (-80± 6 mmHg) that lasted approximately 10 min. The pressor responses suggest that the vasoconstrictor ETB-like receptors are present in cynomolgus monkeys. 4 The data suggest the presence of two distinct vasoconstrictor ET receptor subtypes on smooth muscle cells. The ETA receptors are primarily located on the high pressure side of the circulation. The vasoconstrictor ETB-like receptors appear to be concentrated on the low pressure side.

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The kinetics of the transepithelial movement of heavy metals were studied in the perfused rat jejunum in situ. The peak appearance time (TET) of Zn, Ni, and Cd in portal venous blood was determined after their transient (10 s) introduction into the intestinal lumen. Observed TET values for these metals were positively correlated with their affinities for metallothionein and agreed with those predicted on the basis of a linear three-compartment model that does not allow for paracellular pathways. Further evidence was provided to support the hypothesis that Cd absorption consists first of Cd binding to negative membrane charges followed by a temperature-dependent internalization step.

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