The role of endogenous angiotensin II in the regulation of renal haemodynamics and proximal fluid reabsorption in the rat.
1. The influence of endogenous angiotensin II (AII) on renal haemodynamics and tubular function was examined by clearance and micropuncture methods in anaesthetized rats during AII receptor blockade with the non-peptide antagonist DuP 753 (50 micrograms kg-1 min-1 i.v.). 2. Mean arterial pressure was reduced slightly (-5 +/- 2 mmHg) while filtration fraction and glomerular filtration rate rose by 30% without changes in renal plasma flow (RPF) or renal vascular resistance (RVR). 3. Fractional proximal fluid reabsorption (calculated from lithium clearance) fell from 73 to 64% (P < 0.01) and fractional distal sodium reabsorption decreased from 98 to 94% (P < 0.01). 4. Urine flow rate more than doubled, sodium output increased 4-fold and plasma renin concentration rose 8-fold while potassium excretion remained unchanged. 5. Proximal tubular fluid reabsorption (Jv) as measured by shrinking split-droplet micropuncture decreased by 21% (P < 0.01) during infusion of DuP 753 compared with 22.5% (P < 0.01) during converting enzyme inhibition by enalaprilat (MK422). 6. Responses to DuP 753 were similar to those previously documented with converting enzyme inhibitors except that DuP 753 failed to raise RPF. It is concluded that generation of intrarenal vasodilator paracrines has confounded conclusions about the renal action of converting enzyme inhibitors and we propose that in anaesthetized rats, endogenous angiotensin II (AII) has its major renal influences on glomerular filtration and proximal fluid reabsorption with little effect on renal vascular resistance.
Zhuo
J
J
Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
Thomas
D
D
Harris
P J
PJ
Skinner
S L
SL
D000042:Absorption; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000502:physiology*; D007684:Kidney Tubules / Q000378:metabolism; D019808:Losartan; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology
D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan