(Hypertension. 1999;34:843-847.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Cyclooxygenase-2 Modulates Afferent Arteriolar Responses to Increases in Pressure
From the Department of Physiology, Tulane University School of Medicine, New Orleans, La.
Correspondence to Atsuhiro Ichihara, MD, PhD, Kawasaki City Ida Hospital, Internal Medicine, 2-27-1 Ida, Nakahara-ku, Kawasaki, Kanagawa 211-0035, Japan.
Abstract—This study was designed to examine the contribution of cyclooxygenase-2 (COX-2) in the afferent arteriolar autoregulatory responses to increases in perfusion pressure and its relationship with neuronal nitric oxide synthase (nNOS). In rat kidneys, afferent arteriolar diameter responses to increases in perfusion pressure were assessed in vitro with the blood-perfused juxtamedullary nephron technique. Basal afferent arteriolar diameter at 100 mm Hg averaged 21.0±1.2 µm (n=7), and the vasoconstrictor response to increasing perfusion pressure to 160 mm Hg averaged 18.4±1.2%. Superfusion with the COX-2 inhibitor NS398 (10 µmol/L) did not influence basal diameters, but it did significantly enhance the vasoconstrictor response to the increase in perfusion pressure (32.9±4.0%). In contrast to previous findings that the nNOS inhibitor S-methyl-L-thiocitrulline (10 µmol/L) enhanced afferent arteriolar autoregulatory responses in normal rat kidneys, in this study, administration of 10 µmol/L S-methyl-L-thiocitrulline did not further modulate the vasoconstrictor response to increases in perfusion pressure in the NS398-treated kidneys of normal rats (31.8±4.7%). When tubuloglomerular feedback activity was interrupted by papillectomy and the addition of 50 µmol/L furosemide to the blood perfusate (n=5 for each), the afferent arteriolar constrictor responses to increasing perfusion pressure to 160 mm Hg averaged 7.9±0.9% and 10.7±0.7%, respectively, and they were significantly attenuated compared with the responses observed in control kidneys. NS398 treatment did not modulate the afferent arteriolar autoregulatory responses in papillectomized or furosemide-treated kidneys. These results indicate that COX-2–derived metabolites contribute to the nNOS modulation of pressure-mediated afferent arteriolar autoregulatory responses.
Key Words: autoregulation • neuronal nitric oxide synthase • macula densa • papillectomy • furosemide
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