Influence of chronic angiotensin II infusion on kidney function and intrarenal angiotensin II levels in rats
Description
Angiotensin II (ANG II) is known to play an important physiological role in the blood pressure and body fluid homeostasis mainly via its subtype 1 (AT1) receptors. Chronic infusions of angiotensin II at doses that are initially subpressor can enhance the pressor response to angiotensin II and lead to a slowly developing pressor effect, elevations of intrarenal angiotensin II levels and reductions in renal renin content and renin mRNA. The elevated circulating and intrarenal angiotensin II levels exert substantial influences on renal hemodynamics and excretory function and prevent the kidney from exerting its antihypertensive action via pressure-diuresis and -natriuresis function. Thus, the present study was designed to test the hypothesis that chronic infusion of subpressor doses of angiotensin II causes changes in proximal tubular angiotensin II concentrations, renal hemodynamic and excretory function that can be reversed by blockade of AT1 receptors. The blood pressure and renal functional responses to chronic and acute blockade of AT1 receptors by losartan were evaluated in ANG II-infused hypertensive rats. The autoregulatory capability of renal blood flow (RBF) and glomerular filtration rate (GFR) and renal arterial pressure-natriuresis relationships were assessed in ANG II-infused rats with and without chronic losartan treatment. The intrarenal and proximal tubular angiotensin II concentrations were also measured in ANG II-induced hypertensive rats. ANG II-induced hypertension was associated with a reduced GFR which could not be completely restored by acute losartan administration. In contrast, chronic losartan treatment prevented the decreases in GFR along with the increases in arterial pressure. The autoregulatory capability of RBF and GFR, but not medullary blood flow (MBF), was impaired in ANG II-infused hypertensive rats. The renal arterial pressure-natriuresis and -diuresis curves were shifted to the right. Chronic losartan treatment prevented the impairment of autoregulation of RBIF and GFR, and improved the pressure-natriuresis and -diuresis relationships. In spite of the hypertension, the proximal tubular fluid angiotensin II concentrations in ANG II-infused rats were not significantly different from hose found in normotensive control rats. These data suggest that chronic angiotensin II infusions lead to alterations in renal hemodynamics and excretory function, impaired autoregulation of RBF and GFR, but not MBF, and a rightward shift of the pressure-natriuresis relationship. These renal function changes contribute to the development of hypertension of this model