Vascular and excretory effects of angiotensin II in the rat isolated perfused kidney: influence of an AT1 and a nonselective AT receptor antagonist.

Angiotensin II (AII) is a potent vasoconstrictor which, at physiological plasma concentrations, produces antinatriuresis, whereas high intrarenal concentrations cause natriuresis and diuresis. We examined the effects of a selective AT1 receptor antagonist, losartan, and a nonselective AT receptor antagonist, Sar1Thr8AII, on the response to infusion of AII in the isolated rat kidney perfused at constant pressure with a recirculating modified Krebs-Henseleit buffer. AII increased renal vascular resistance (RVR), glomerular filtration rate (GFR) and urinary volume (UV) and sodium excretion (UNaV) without changing the fractional excretion of water or electrolytes.

Analysis of eicosanoid mediation of the renal functional effects of hyperchloremia.

Depression of GFR and antinatriuresis in response to high chloride has been linked to a cyclooxygenase (COX)-dependent mechanism involving thromboxane A2 (TxA2) and prostaglandin endoperoxide (PGH2), because inhibition of COX prevented the fall in GFR and antinatriuresis produced by hyperchloremia. However, hyperchloremia did not increase, but unexpectedly decreased, renal prostaglandin and TxA2 efflux (Yin et al., 1995).

Association between the natriuretic action of angiotensin-(1-7) and selective stimulation of renal prostaglandin I2 release.

We previously reported that angiotensin-(1-7) [Ang-(1-7)], a heptapeptide derived from the metabolism of either Ang I or Ang II, was biologically active in the rat isolated kidney, producing a marked diuresis and natriuresis that could be dissociated from the modest increase in glomerular filtration rate. The natriuretic response was accompanied by an increase in sodium concentration and concomitant decrease in urinary potassium concentration. Ang-(1-7) has also been shown to stimulate arachidonic acid release from isolated proximal tubules and elicit prostaglandin release from a number of tissues.

Role of chloride in the variable response of the kidney to cyclooxygenase inhibition.

The role of prostanoids in renal function remains unclear, as inhibitors of cyclooxygenase (COX) have contrasting effects. We postulated that these inconsistencies were related to differential effects of the prevailing chloride concentration on COX-dependent mechanisms. In oncotically perfused rat kidneys, in the presence of either high (117 mM) or low (87 mM) chloride with sodium held constant, low chloride resulted in a higher glomerular filtration rate (GFR) than with high chloride, i.

Natriuretic action of angiotensin(1-7).

Evidence that angiotensin(1-7) (Ang(1-7)) is biologically active and can be synthesized by the kidney prompted us to examine its actions in the rat, isolated kidney. Ang(1-7) had three major effects producing, (1) a substantial natriuresis and diuresis, (2) an increase in urinary sodium concentration associated with a fall in potassium concentration and (3) an increase in glomerular filtration rate without affecting renal vascular resistance. Thus, Ang(1-7) may participate in the renal effects of the renin-angiotensin system.