Subpressor infusions of angiotensin II alter glomerular binding, prostaglandin E2, and cyclic AMP production.

Abstract

SUMMARY Angiotensin II (ANG II)Portions of this work were presented at the American Society of Nephrology, December 1982 and 1984, and published in abstract form (Kidney Int 1983;23:277 and 1985;27:256).Address for reprints: Dr. Janice Green Douglas, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106. tration coefficient (K f ) through this action. 6 -7 In certain experimental models of kidney disease, the observed decreases in K { and nephron filtration rate have been postulated to occur in part secondary to increased circulating ANG II. A pathogenetic role for ANG II has been substantiated by the observation that a decrease in the intrarenal concentration of ANG II significantly minimizes the alterations in glomerular function.8 " 10Although pharmacological concentrations of ANG II decrease glomerular ANG II receptor density, it is not clear whether there is an accompanying decrease in the ^-lowering effect of ANG I I . " 1 2 It is also unclear whether a more modest elevation of ANG II has the same effect on binding or function. For example, mercuric chloride-induced renal failure associated with a twofold increase in circulating ANG II produces no decrement in glomerular ANG II receptor density.

Angiotensin II stimulation of hydrogen ion secretion in the rat early proximal tubule. Modes of action, mechanism, and kinetics.

“…In the above perfusion experiments in which lumens were perfused with an angiotensin II-free solution, the augmented hydrogen ion secretion after intravenous angiotensin II was signaled via the basolateral route ( 12,14). The systemic angiotensin II level under normal conditions in the rat is -1-5 X 10-12 M and rises to -5-10 X 10-12 M after low-dose intravenous angiotensin II administration (22,23). Since membrane receptors facing the tubular lumen also exist (13,14), occupancy of luminal receptors by comparable doses of angiotensin II might also affect transport.…”

“…These studies assessed the relative physiologic importance of basolateral versus luminal effects. The magnitude of transport stimulation by intravenous angiotensin II (which raises systemic angiotensin II level from about 1-5 to 5-10 X 10-12 M [22,23]) with an angiotensin II-free perfusate was compared to that elicited by luminal perfusion with either 1 X 10-12 M (n = 5) or 1 X 10-" M (n = 5) angiotensin II under conditions of a constant basolateral environment.…”

Angiotensin II stimulates early proximal bicarbonate absorption in the rat by decreasing cyclic adenosine monophosphate.

“…The ability for angiotensin II to depress adenylate cyclase activity and intracellular cAMP level has been described in many tissues (1 1, 12), including liver (13)(14)(15), aorta (16), adrenal cortex (17,18), pituitary (19), and testis (20). In the kidney, this signaling process has been shown in cortical homogenates (21), glomeruli (22,23), juxtaglomerular apparatus (24), tubule suspensions (23), and proximal cells in culture (25). In some of these studies, the necessary intermediation of a G1 protein was demonstrated by showing that the decrement in cAMP evoked by angiotensin II was sensitive to pertussis toxin (13,19,20,24).…”

“…However, when phorbol ester was perfused in the in vitro rabbit PCT to activate protein kinase C, bicarbonate transport was actually inhibited (10). Another signaling system used by angiotensin II in many cells (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) including those of the PCT (25) involves reduction of adenylate cyclase activity to lower intracellular cAMP concentration. No correlation with renal epithelial cell ion transport has been yet made with this angiotensin II signaling mode.…”

Renal angiotensin receptor mapping in obese spontaneously hypertensive rats.

“…The downregulation of Ang II receptors in the medulla may be a reflection of events within the glomerulus controlling Ang II production. Because Ang II can upregulate its own receptor within the kidney, 23 we cannot yet be certain whether downregulation in obese SHR was due to excess Ang II or a relative lack of Ang II. Receptors for Ang II have not previously been characterized in an experimental model of nephritis.…”