Relationship between basal NO release and cyclooxygenase products in the normal rat kidney.
We investigated the physiological regulation of renal function by nitric oxide (NO) and its interactions with the endothelial cyclooxygenase products in the conscious, chronically catheterized rat. A subpressor dose of NO inhibitor nitro-L-arginine methyl ester (L-NAME) produced renal vasoconstriction that was unaffected by cyclooxygenase inhibition with indomethacin (Indo). Acute, high-dose L-NAME produced a pressor response of approximately 40 mmHg and marked renal vasoconstriction. Indo selectively amplified the renal vasoconstriction, whereas inhibition of the thromboxane-endoperoxide receptor had no effect. Chronic NO inhibition for 5 wk led to sustained hypertension and renal vasoconstriction; the latter was amplified by acute Indo. These data suggest that in the normal, conscious rat the kidney is under important NO-dependent tone. There is no obvious interaction between NO and the cyclooxygenase products in control of basal renal function. When systemic NO inhibition is produced with either acute or chronic high-dose L-NAME, the kidney is severely vasoconstricted. The renal vasoconstriction is not ameliorated by thromboxane-endoperoxide antagonism but is exacerbated by cyclooxygenase blockade, suggesting that vasodilator cyclooxygenase products compensate for the renal hypoperfusion because of severe NO deficiency.
Baylis
C
C
Department of Physiology, West Virginia University, Morgantown 26506-9229, USA.
Slangen
B
B
Hussain
S
S
Weaver
C
C
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D017482:Receptors, Thromboxane; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin