Importance of nephron number in the regulation of arterial pressure and renal function during ageing

Abstract

The physiological importance of the kidneys in the long-term control of extracellular volume and arterial pressure has been demonstrated in studies showing that an alteration of renal function leads to the development of hypertension and other cardiovascular dysfunctions (1-4). It has also been proposed that the development of hypertension may be secondary to an altered nephron endowment during the nephrogenic period (3,4). A cause-effect link between nephron number at birth and hypertension has been proposed in clinical and experimental studies showing that essential hypertensive patients have a reduced nephron number (3-6), and that the alteration of nephrogenesis leads to the development of hypertension during the adult life (3,4,7-10). A deficient nephrogenesis has been observed in offspring of pregnant mothers taking a low protein diet, or treated with either corticoids or a cyclooxygenase-2 (COX-2) inhibitor (3,4). The renin-angiotensin system (RAS) seems to play an important role in the regulation of nephrogenesis because its activity is reduced in these situations (3,4), and it is known that angiotensin II (Ang II) is involved in regulating renal growth and differentiation (11). The role of Ang II in renal development has been confirmed in studies demonstrating an elevation of all RAS components during the nephrogenic period and showing that the administration of either a converting enzyme inhibitor or an Ang II AT1 receptor antagonist during this period leads to a significant reduction in nephron number and an alteration of the normal kidney structure (7,8).