The effects of nonsteroidal anti-inflammatory drugs on renal function: experimental studies in animals.
Studies in various experimental animal models have been invaluable in delineating the physiological and pathophysiological conditions under which renal prostaglandin (PG) synthesis is a major determinant of renal function; conditions in which the inhibition of renal PG synthesis by the administration of a nonsteroidal anti-inflammatory drug (NSAID) will significantly alter kidney function. This article presents the initial schema or concept that under certain well-defined conditions or disease states, an increase in renal sympathetic adrenergic and/or angiotensin II activity stimulates an increase in the synthesis of vasodilatory PG (PGE2/PGI2) to offset or modulate the vasoconstriction. In these renal "PG-dependent" states, a reduction of renal PG by NSAID administration adversely affects renal function by causing renal vasoconstriction, thus decreasing glomerular filtration and causing the retention of sodium and water. More recent experimental data from animal models are then reviewed to illustrate that the number of conditions or disease states in which renal function is PG-dependent has increased dramatically. Last, evidence is reviewed suggesting that under certain conditions, inherent increases in the synthesis of renal vasodilatory PGE2 and PGI2 and/or vasoconstrictive thromboxane A2 (TxA2) may be occurring. In these situations, renal function would also be more susceptible to NSAID-induced renal vasoconstriction and sodium retention.
Zambraski
E J
EJ
Department of Biological Sciences, Rutgers University, New Brunswick, NJ 08903, USA.
D000375:Aging / Q000502:physiology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins