Nitric oxide buffers renal medullary vasoconstriction induced by prostaglandins synthesis blockade.
The aim of this study was to examine whether nitric oxide (NO) buffers the renal medullary vasoconstriction induced by a prostaglandins (PG) synthesis inhibitor. Daily blood pressure measurements were made with implanted catheters and changes in cortical blood flow (CBF) and medullary blood flow (MBF) were determined by implanted optical fibers and laser-Doppler flow measurement techniques in conscious rats. Sodium and water balance were also determined. Infusion of meclofenamate, a nonisozyme-specific cyclooxygenase (COX) inhibitor, at 5 microg/kg/min over 4 consecutive days (n=12 rats) elicited a transitory increase (p<0.05) in mean arterial pressure (MAP) and a transitory decrease (p<0.05) in MBF and sodium excretion without altering CBF. In contrast, the simultaneous infusion of meclofenamate and N(G)-nitro-L-arginine methyl ester (L-NAME, 0.8 microg/kg/min), a NO synthesis inhibitor, over 4 consecutive days (n=12) produced a continuous increase (p<0.01) in MAP and a continuous decrease (p<0.05) in MBF and sodium excretion without altering CBF. The results of this study suggest that the renal medullary vasoconstrictor effects and sodium retention induced by meclofenamate are enhanced by a subpressor dose of L-NAME, and that NO may buffer the renal medullary vasoconstriction induced by the blockade of PG synthesis in conscious rats.
Nakanishi
K
K
Second Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan. kazunaka@med.toho-u.ac.jp
Chinen
A
A
Saito
Y
Y
Hamada
K
K
Hara
N
N
Nagai
Y
Y
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002021:Buffers; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007275:Injections, Intravenous; D007679:Kidney Medulla / Q000098:blood supply*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014661:Vasoconstriction / Q000502:physiology*
D002021:Buffers; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011448:Prostaglandin Antagonists; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D019331:NG-Nitroarginine Methyl Ester