Cyclooxygenase-2 Modulates Afferent Arteriolar Responses to Increases in Pressure

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1999-10, Vol.34 (4, Part 2), p.843-847
• Main Authors: Ichihara, Atsuhiro, Imig, John D, Navar, L Gabriel
• Format: Article
• Language: English
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Cardiology. Vascular system; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Experimental diseases; Isoenzymes - physiology; Kidney - blood supply; Kidney - physiology; Male; Medical sciences; Nitrobenzenes - pharmacology; Prostaglandin-Endoperoxide Synthases - physiology; Rats; Rats, Sprague-Dawley; Renal Circulation - drug effects; Renal Circulation - physiology; Sulfonamides - pharmacology
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.34.4.843

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.