S. Shastri et al., Cysteinyl leukotrienes mediate enhanced vasoconstriction to angiotensin IIbut not endothelin-1 in SHR, AM J P-HEAR, 281(1), 2001, pp. H342-H349
Citations number
36
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
We assessed whether cysteinyl leukotrienes mediate the vasoconstrictor resp
onses to angiotensin II and endothelin-1 in the mesenteric vascular bed of
Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) perfused ex vi
vo at a constant flow rate of 5 ml/min with Krebs buffer. Maximal perfusion
pressure response (E-max) but not EC50 values to angiotensin II (P<0.001)
and endothelin-1 (P<0.01) were significantly higher in the SHR, whereas the
responses to potassium chloride remained unchanged. Inclusion of the selec
tive 5-lipoxygenase inhibitor AA-861 or the cysteinyl leukotriene receptor
antagonist MK-571 significantly reduced the vasoconstrictor responses to an
giotensin II but not to endothelin-1 and potassium chloride. The reduction
in Emax to angiotensin II was more pronounced in SHR (P<0.001) than in WKY
(P<0.05) rats. Cysteinyl leukotrienes LTC4-, LTD4-, and LTE4 (1 muM)-evoked
vasoconstrictor responses were significantly higher in SHR (P<0.05), where
as LTB4 failed to evoke any response in either strain. These data suggest t
hat 5-lipoxygenase metabolites, particularly cysteinyl leukotrienes, contri
bute to the exaggerated vasoconstrictor responses to angiotensin II but not
to endothelin-1.