Increased renal vasoconstriction and gene expression of cyclooxygenase-1 in renovascular hypertension.
Vascular responses to arachidonic acid (AA) in the renal circulation are increased in hypertensive rats. We have suggested that these differences are related to changes in AA metabolism. In this study we investigated the mechanism involved in the increased AA-induced renal vasoconstriction. We evaluated vascular renal reactivity in the isolated perfused kidney, cyclooxygenase activity, protein content, and mRNA expression of kidneys from sham operated and aortic coarctation rats. Bolus injection of AA (1, 2, 4, and 8 microg) increased perfusion pressure in a dose-dependent manner by 20 +/- 4, 28 +/- 5, 38 +/- 6, and 44 +/- 7 mm Hg in sham-operated rats and 30 +/- 3, 55 +/- 5, 78 +/- 5, and 113 +/- 8 mm Hg in rats with aortic coarctation. Indomethacin (1 microg/ml) or the endoperoxide/thromboxane blocker SQ29548 (1 microM) prevented AA renal vasoconstriction. Cyclooxygenase activity, cyclooxygenase-1 protein content, and mRNA expression were also increased in the renal tissue from the aortic coarctation rats compared with sham-operated rats. In conclusion, we suggest that during development of hypertension, the cyclooxygenase-1 mRNA is induced, and consequently cyclooxygenase-1 activity and AA metabolism are increased, resulting in augmented production of vasoconstrictor prostaglandins that mediate the potentiated responsiveness to AA or other vascular agonists that release AA, thus increasing peripheral vascular resistance.
Vazquez-Cruz
B
B
Division of Investigation, Escuela National de Estudios Profesionales Iztacala UNAM, Tlalnepantla, Mexico.
Lopez
P
P
Talamas-Rohana
P
P
Escalante
B
B
D000818:Animals; D001017:Aortic Coarctation; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D006977:Hypertension, Renal / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism*; D012313:RNA / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013929:Thromboxane B2 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
D016718:Arachidonic Acid; D013929:Thromboxane B2; D012313:RNA; D011451:Prostaglandin-Endoperoxide Synthases