Lithium pretreatment affects renal and systemic responses to angiotensin II infusion in normal man

Abstract

1. Renal and systemic responses to infusion of angiotensin II (1.25 and 2.5 ng min-1 kg-1 body weight) were examined in ten normal males 12 h after single doses of 750 mg of lithium carbonate, 250 mg of lithium carbonate (n = 6) or placebo. 2. Baseline mean arterial pressure [mean (SEM)] was higher after 750 mg of lithium [93.1 (1.7) versus 89.5 (1.9 mmHg, P = 0.014], and the subsequent rise in blood pressure during angiotensin II infusion was lower [8.2 (1.8) versus 12.2 (2.4) mmHg, P less than 0.02]. 3. Lithium at a dose of 750 mg increased overnight urinary sodium excretion before the study. The fall in fractional sodium excretion during angiotensin II infusion was reduced after pretreatment with 750 mg of lithium [750 mg of lithium, 2.73 (0.24) to 1.34 (0.08)%; placebo, 2.69 (0.26) to 1.01 (0.11)%; P = 0.02]. The increases in effective filtration fraction [750 mg of lithium, 5.4 (1.0)%; placebo, 8.6 (0.7)%; P less than 0.05] and total effective renal vascular resistance [750 mg of lithium, 3700 (390) dyn s cm-5; placebo 5100 (460) dyn s cm-5; P = 0.03] during angiotensin II infusion were also attenuated after 750 mg of lithium. Responses after 250 mg of lithium did not differ from those after placebo. 4. The fall in plasma renin activity and the increase in plasma aldosterone concentration during angiotensin II infusion were similar on each study day. 5. Renal responses to exogenous angiotensin II are altered after pretreatment with a 750 mg dose of lithium in normal man. This dose of lithium is not an inert marker of sodium handling.

The Renal Microcirculation

“…At the lower doses, RBF may decrease without changes in GFR or even with slight increases in GFR [1084] . Ang II infusions to humans elicit greater reductions in RBF in high sodium subjects than in the low sodium subjects; however, GFR is not significantly altered in either group [1085,1086] . Ang II infusions to humans elicit greater reductions in RBF in high sodium subjects than in the low sodium subjects; however, GFR is not significantly altered in either group [1085,1086] .…”

“…Similar responses result from low chronic doses infused directly into the renal artery for up to 5 days [759] . In other studies, Ang II infusion at 1, 4 and 8 pmol/kg/min into subjects maintained on high salt intake (340 mM) and taking enalapril to reduce endogenous Ang II levels [1085,1087,1088] , produced greater decreases in RBF than in GFR, but both decreased. In other studies, Ang II infusion at 1, 4 and 8 pmol/kg/min into subjects maintained on high salt intake (340 mM) and taking enalapril to reduce endogenous Ang II levels [1085,1087,1088] , produced greater decreases in RBF than in GFR, but both decreased.…”

Angiotensin II attenuates the natriuresis of water immersion in humans

“…The effect of lithium pretreatment on U Na V has been debated for several years (12,33,42). To approach reliable plasma concentrations of Li for precise and accurate measurements, a test dose of 450 mg LiCO 3 was used in protocol 2 (46).…”

The natriuretic effect of lithium in man: Is the proximal tubule involved?

“…Previous studies in humans have also shed little light on the issue. Eadington et al [ 5 ] found that CLi following ingestion of 750 mg lithium carbonate was the same as that following a 250 mg dose. However, at the time clearances were performed, no natriuresis was apparent with either dose.…”