C G Duarte1, J Zhang, S Ellis. 1. Division of Cardio-Renal Drug Products, Food and Drug Administration, Rockville, Maryland 20857, USA.
Abstract
RATIONALE AND OBJECTIVES: The purpose of this research was to study the effects of the radiocontrast medium (CM) Hypaque-76 (diatrizoate meglumine sodium), equiosmolar mannitol, and endothelin on blood pressure and renal damage in a aging male spontaneously hypertensive rat, a small animal model for CM-induced renal damage. The importance of the pressor effect and the high osmolality of CM in producing renal damage was investigated by first reducing the blood pressure with pentobarbital anesthesia, which suppresses sympathetic nervous system activity, then testing the effects of CM, saline, mannitol, and the potent vasoconstrictor endothelin alone and in combination with CM. METHODS: Systolic blood pressure was measured in 14-month-old male rats (1) when awake, (2) after pentobarbital anesthesia, (3) after the administration of saline, CM, mannitol, endothelin, or CM plus endothelin, (4) after awakening the same day, and (5) the following day while awake. Renal damage was quantified by evaluating histopathologically the left kidney removed the day after administration of test substances. RESULTS: The pentobarbital-lowered blood pressure remained depressed after saline and mannitol but rose dramatically after CM, endothelin, and CM plus endothelin. Renal damage, compared with the saline controls, occurred with CM, mannitol, endothelin, and endothelin plus CM. The order of increasing severity was mannitol = CM < endothelin < endothelin plus CM. CONCLUSIONS: The effect of CM on systolic blood pressure is not related to its osmolality. High osmolality, however, appears to be a factor in CM-induced renal damage. Ischemia and direct nephrotoxicity are factors contributing to the renal-damaging effects of CM, mannitol, and endothelin.
RATIONALE AND OBJECTIVES: The purpose of this research was to study the effects of the radiocontrast medium (CM) Hypaque-76 (diatrizoate meglumine sodium), equiosmolar mannitol, and endothelin on blood pressure and renal damage in a aging male spontaneously hypertensiverat, a small animal model for CM-induced renal damage. The importance of the pressor effect and the high osmolality of CM in producing renal damage was investigated by first reducing the blood pressure with pentobarbital anesthesia, which suppresses sympathetic nervous system activity, then testing the effects of CM, saline, mannitol, and the potent vasoconstrictor endothelin alone and in combination with CM. METHODS: Systolic blood pressure was measured in 14-month-old male rats (1) when awake, (2) after pentobarbital anesthesia, (3) after the administration of saline, CM, mannitol, endothelin, or CM plus endothelin, (4) after awakening the same day, and (5) the following day while awake. Renal damage was quantified by evaluating histopathologically the left kidney removed the day after administration of test substances. RESULTS: The pentobarbital-lowered blood pressure remained depressed after saline and mannitol but rose dramatically after CM, endothelin, and CM plus endothelin. Renal damage, compared with the saline controls, occurred with CM, mannitol, endothelin, and endothelin plus CM. The order of increasing severity was mannitol = CM < endothelin < endothelin plus CM. CONCLUSIONS: The effect of CM on systolic blood pressure is not related to its osmolality. High osmolality, however, appears to be a factor in CM-induced renal damage. Ischemia and direct nephrotoxicity are factors contributing to the renal-damaging effects of CM, mannitol, and endothelin.