Renal effects of prolonged cyclooxygenase inhibition when angiotensin II levels are elevated.
We examined the renal functional and hemodynamic changes induced by prolonged cyclooxygenase (COX) inhibition when angiotensin II levels are elevated during several consecutive days. The effects induced by the infusion of either initially subpressor or pressor angiotensin II doses (1 and 5 ng/kg/min) were examined in dogs with or without the simultaneous infusion of meclofenamate (5 microg/kg/min). Experiments were performed in conscious permanently instrumented dogs. Infusion of the lower angiotensin II dose alone (n = 6) caused a late 12+/-2% increase in arterial pressure, a 25+/-6% decrease in renal blood flow (RBF), and a transitory decrease in urinary sodium excretion. COX inhibition reduced the hypertension and renal vasoconstriction, but enhanced the sodium retention, induced by the lower dose angiotensin II infusion (n = 6). The higher angiotensin II dose (n = 6) caused a 25+/-4% increase in arterial pressure, a 24+/-5% decrease in RBF, and a transitory decrease in urinary sodium excretion. Finally, COX inhibition did not modify the renal effects elicited by the higher angiotensin II dose (n = 6). The results of this study suggest that endogenous prostaglandins play an important role in the regulation of the renal and systemic changes induced by prolonged administration of initially subpressor angiotensin II doses. It has also been demonstrated that prolonged COX inhibition does not modify the renal functional and hemodynamic changes elicited by the long-term infusion of a pressor angiotensin II dose.
González
J D
JD
Departamento de Fisiología, Facultad de Medicina, Murcia, Spain.
Llinás
M T
MT
Moreno
C
C
Rodríguez
F
F
Salazar
F J
FJ
D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000294:innervation*; D012079:Renal Circulation / Q000187:drug effects*; D012964:Sodium / Q000652:urine; D013564:Sympathetic Nervous System / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D000804:Angiotensin II; D012964:Sodium