Effects of angiotensin II on renal sodium handling and diluting capacity in man pretreated with high-salt diet and enalapril.
The antinatriuretic effect of angiotensin II (Ang II) is generally attributed to a decreased glomerular filtration rate (GFR) and an increased proximal tubular sodium reabsorption. We studied this by infusion of increasing amounts (1, 4, and 8 pmol/kg per min) of Ang II in seven water-loaded volunteers who were pretreated with enalapril and a high-salt diet. While mean arterial pressure increased from 92 +/- 3 mmHg to respectively 98 +/- 3, 110 +/- 2, and 116 +/- 2 mmHg, sodium excretion fell from 331 +/- 40 to 135 +/- 23, 65 +/- 17, and 63 +/- 22 mumol/min, and GFR from 138 +/- 9 to 128 +/- 6, 111 +/- 6, and 104 +/- 8 ml/min (P < 0.05 for each variable). At 1 pmol/kg per min, Ang II decreased maximal urine flow and the fractional excretions of lithium and uric acid. Urine sodium concentration decreased, whereas minimal urine osmolality remained unchanged. At 4 pmol/kg per min, these effects were more pronounced. Moreover, minimal urine osmolality increased from 58 +/- 4 to 72 +/- 8 mosm/kg, but sodium concentration decreased further. The step to 8 pmol/kg per min did not decrease sodium, lithium, or uric acid excretion further, but induced a further increase in minimal urine osmolality to 99 +/- 16 mosm/kg. These data suggest that the antinatriuretic effect of modestly hypertensive dosages of Ang II is not only due to a decrease in GFR and an increase in proximal sodium reabsorption, but also involves a rise in fractional reabsorption in a distal nephron segment. In addition Ang II decreases renal diluting capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
Vos
P F
PF
Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
Koomans
H A
HA
Boer
P
P
Dorhout Mees
E J
EJ
D000804:Angiotensin II / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism*; D012982:Sodium, Dietary / Q000008:administration & dosage*
D012982:Sodium, Dietary; D000804:Angiotensin II; D004656:Enalapril; D012964:Sodium; D012083:Renin