Faculty Collaboration Database

Cyclooxygenase-2 modulates afferent arteriolar responses to increases in pressure. Hypertension 1999 Oct;34(4 Pt 2):843-7

Date

10/16/1999

Pubmed ID

10523371

DOI

10.1161/01.hyp.34.4.843

Scopus ID

2-s2.0-0032711842 (requires institutional sign-in at Scopus site)   52 Citations

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 microm (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 micromol/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 micromol/L) enhanced afferent arteriolar autoregulatory responses in normal rat kidneys, in this study, administration of 10 micromol/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 micromol/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.

Author List

Ichihara A, Imig JD, Navar LG

MESH terms used to index this publication - Major topics in bold

Animals
Blood Pressure
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Isoenzymes
Kidney
Male
Nitrobenzenes
Prostaglandin-Endoperoxide Synthases
Rats
Rats, Sprague-Dawley
Renal Circulation
Sulfonamides