Synergistic intrarenal actions of angiotensin on tubular reabsorption and renal hemodynamics.
There is a growing awareness that the direct intrarenal actions of angiotensin II (ANG II) on both tubular and vascular structures contribute to sodium conservation. Even very low concentrations of ANG II (10(-1)) mol/L) stimulate proximal reabsorption rate. Recent studies indicate that this stimulatory action is due to an enhanced activity of the sodium/hydrogen exchanger of the luminal membrane. Elevated ANG II levels in the renal interstitium, effected either through increased delivery of ANG II via the circulation or as a consequence of conversion of angiotensin I (ANG I) generated locally, can also enhance proximal reabsorption rate. One consequence of enhanced proximal reabsorption rate is reduced distal volume delivery, which would be expected to elicit arteriolar vasodilation mediated by the tubuloglomerular feedback (TGF) mechanism. It has been observed, however, that peritubular capillary infusions of either ANG I or ANG II, at doses sufficiently low to be without obvious direct effects on glomerular dynamics, can increase the sensitivity of the TGF mechanism. This enhanced TGF sensitivity serves to minimize or prevent TGF mediated increases in glomerular filtration rate in the face of reduced distal delivery. With greater increases in interstitial ANG II concentration, reductions in glomerular pressure have been observed, demonstrating a powerful action on preglomerular arterioles that predominates over the well known effects on efferent arterioles. At these higher doses, the direct hemodynamic actions of ANG II, plus the effects on the glomerular filtration coefficient, will directly reduce filtered sodium load. Through these synergistic effects on both tubular reabsorptive and hemodynamic function, ANG II can elicit sustained decreases in distal nephron sodium delivery which contribute greatly to its efficacy as a regulator of sodium excretion.
Navar
L G
LG
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana.
Saccomani
G
G
Mitchell
K D
KD
D000042:Absorption; D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*
D000804:Angiotensin II