EFFECTS OF INDOMETHACIN ON THE REGIONAL HEMODYNAMIC-RESPONSES TO LOW-DOSES OF ENDOTHELINS AND SARAFOTOXIN

1. Regional haemodynamic responses to i.v. bolus injections of low doses (4 pmol and 40 pmol) of endothelin-1, -2, -3 and sarafotoxin-S6b were assessed in conscious, Long Evans rats in the absence and presence of indomethacin. 2. Both doses of endothelin-3 and sarafotoxin-S6b caused early renal vasodilatations that were not affected by indomethacin. Endothelin-1 caused an initial renal vasodilatation only in the presence of indomethacin, indicating that this peptide produced concurrent release of cyclo-oxygenase products that caused renal vasoconstriction. Neither dose of endothelin-2 produced an increase in renal conductance. 3. The 4 pmol dose of all four peptides caused mesenteric vasoconstrictions only. With the 40 pmol dose of the peptides, none caused early mesenteric vasoconstriction except in the presence of indomethacin. Thus, in this vascular bed the primary vasoconstrictor effects of the peptides (seen with the 4 pmol dose) were offset, following the 40 pmol dose, by release of vasodilator cyclo-oxygenase products. Indomethacin alone caused significant vasoconstriction only in the mesenteric vascular bed, indicating that in this region of the circulation, vasodilator prostanoids might be involved also in the tonic control of vascular conductance. 4. All four peptides at both doses caused early hindquarters vasodilatation. However, only the initial hypotensive and hindquarters vasodilator effects of the 40 pmol dose of sarafotoxin-S6b were attenuated by indomethacin. Under these conditions the hindquarters vasodilator effects of sarafotoxin-S6b were similar to those of the other peptides, indicating that the more marked effects of sarafotoxin-S6b in the absence of indomethacin were contributred to by vasodilator cyclo-oxygenase products in the hindquarters.