Effects of verapamil on the renal actions induced by nitric oxide and prostaglandin synthesis inhibition.
This study was designed to determine the effects of a calcium antagonist (verapamil) on the renal actions induced by nitric oxide synthesis inhibition, with and without simultaneous prostaglandin synthesis inhibition. The renal effects of verapamil (2 micrograms/kg/min) were examined in anesthetized dogs before and after an increase of extracellular volume and during the reduction of nitric oxide synthesis (1 microgram/kg/min NG-nitro-L-arginine methyl ester [L-NAME]), with and without the administration of a cyclooxygenase inhibitor (5 micrograms/kg/min meclofenamate). Nitric oxide synthesis inhibition produced an increase in proximal sodium reabsorption (lithium clearance technique) and a decrease in the excretory response to volume expansion that was prevented by the administration of verapamil. The administration of a cyclooxygenase inhibitor, during nitric oxide synthesis inhibition, elicited an increase in arterial pressure, an important renal vasoconstriction, and reduced the renal excretory response to volume expansion. The antinatriuretic effect produced by the simultaneous reduction of nitric oxide and prostaglandin synthesis, before and after the volume expansion, was abolished with the verapamil infusion. However, the increase of arterial pressure and renal vasoconstriction were only partly affected by verapamil. We found that the antinatriuretic effect secondary to the reduction of nitric oxide synthesis, during an increase in extracellular volume, is prevented by the administration of verapamil. Additionally, the administration of verapamil completely prevents the antinatriuretic, but not the vasoconstrictor, effects induced by the administration of a cyclooxygenase inhibitor when nitric oxide is slightly reduced.
Departamento de Fisiologia, Faculted de Medicina, Murcia, Spain.
M T
MT
Llinás
J D
JD
González
F J
FJ
Salazar
D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D004285:Dogs; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006977:Hypertension, Renal / Q000139:chemically induced / Q000517:prevention & control*; D007261:Infusions, Intra-Arterial; D008469:Meclofenamic Acid / Q000008:administration & dosage; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D011448:Prostaglandin Antagonists / Q000008:administration & dosage; D014700:Verapamil / Q000008:administration & dosage*
D002121:Calcium Channel Blockers; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011448:Prostaglandin Antagonists; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D014700:Verapamil; D019331:NG-Nitroarginine Methyl Ester