Long-Term Consequences of Uninephrectomy in Male and Female Rats

Prenatal ethanol exposure is teratogenic, but the effects of ethanol on kidney development and the health of offspring are incompletely understood. Our objective was to investigate the effects of acute ethanol exposure during pregnancy on nephron endowment, mean arterial pressure, and renal function in offspring. We administered ethanol or saline by gavage to pregnant Sprague-Dawley rats on embryonic days 13.5 and 14.5. At 1 month of age, the nephron number was 15% lower and 10% lower in ethanol-exposed males and females, respectively, compared with controls. Mean arterial pressure, measured in conscious animals via indwelling tail-artery catheter, was 10% higher in both ethanol-exposed males and females compared with controls. GFR was 20% higher in ethanol-exposed males but 15% lower in ethanol-exposed females; moreover, males had increased proteinuria compared with controls. Furthermore, embryonic kidneys cultured in the presence of ethanol for 48 hours had 15% fewer ureteric branch points and tips than kidneys cultured in control media. Taken together, these data demonstrate that acute prenatal ethanol exposure reduces the number of nephrons, possibly as a result of inhibited ureteric branching morphogenesis, and that these changes affect adult cardiovascular and renal function.

In all forms of chronic hypertension, the renal-pressure natriuresis mechanism is abnormal because sodium excretion is the same as in normotension despite the increased blood pressure. However, the importance of this resetting of pressure natriuresis as a cause of hypertension is controversial. Theoretically, a resetting of pressure natriuresis could necessitate increased blood pressure to maintain sodium balance or it could occur secondarily to hypertension. Recent studies indicate that, in several models of experimental hypertension (including angiotensin II, aldosterone, adrenocorticotrophic hormone, and norepinephrine hypertension), a primary shift of renal-pressure natriuresis necessitates increased arterial pressure to maintain sodium and water balance. In genetic animal models of hypertension, there also appears to be a resetting of pressure natriuresis before the development of hypertension. Likewise, essential hypertensive patients exhibit abnormal pressure natriuresis, although the precise cause of this defect is not clear. It is likely that multiple renal defects contribute to resetting of pressure natriuresis in essential hypertensive patients. With long-standing hypertension, pathological changes that occur secondary to hypertension must also be considered. By analyzing the characteristics of pressure natriuresis in hypertensive patients and by comparing these curves to those observed in various forms of experimental hypertension of known origin, it is possible to gain insight into the etiology of this disease.