Effects of indomethacin and iloprost on contraction of the afferent arterioles by endothelin-1 in juxtamedullary nephron preparations from normotensive Wistar-Kyoto and spontaneously hypertensive rats.
The contractile effects of endothelin-1 on the afferent arterioles of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) and the modulation of these responses by cyclooxygenase blockade or by the prostacyclin analog iloprost were investigated. For this, the preglomerular vasculature was visualized by using the juxtamedullary nephron preparation. Endothelin-1 (100 pM-1 microM) induced concentration-dependent reduction of afferent diameters either in WKY and SHR kidneys, which were inhibited by 1 microM nifedipine, indicating its dependence on extracellular calcium. After incubation with 20 microM indomethacin, the endothelin-1-induced contractions were potentiated in WKY but abolished in SHR vessels. These results could be explained if endothelin-1 is releasing vasodilator prostanoids in WKY, whereas in SHR preparations, vasoconstrictor prostanoids predominate. The prostacyclin analog iloprost (1 nM-1 microM) did not modify basal diameters of the WKY afferent arterioles, whereas a weak vasodilatatory effect was observed in the SHR afferent vasculature. Both in WKY and SHR preparations, iloprost (10 nM-1 microM) abolished the afferent contractility by endothelin-1, this effect being more prominent in SHR. We conclude that a defective production of vasodilator prostanoids or an enhanced release of vasoconstrictor cyclooxygenase derivatives may determine the renovascular effects of endothelins in SHR kidneys.
González
M R
MR
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Villa
E
E
García-Robles
R
R
Angulo
J
J
Peiró
C
C
Marín
J
J
Sánchez-Ferrer
C F
CF
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D019332:Endothelin-1 / Q000494:pharmacology*; D016285:Iloprost / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D009399:Nephrons / Q000098:blood supply* / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction; D014665:Vasodilator Agents / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D019332:Endothelin-1; D014665:Vasodilator Agents; D016285:Iloprost; D007213:Indomethacin