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

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 < 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 < 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.

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Acute and chronic actions of bradykinin on renal function and arterial pressure

AJP Renal Physiology ◽

10.1152/ajprenal.1985.248.1.f87 ◽

1985 ◽

Vol 248 (1) ◽

pp. F87-F92 ◽

Cited By ~ 5

Author(s):

J. P. Granger ◽

J. E. Hall

Keyword(s):

Arterial Pressure ◽

Renal Plasma Flow ◽

Urine Volume ◽

Plasma Renin ◽

Urinary Sodium Excretion ◽

Renal Perfusion ◽

Acute Effects ◽

Plasma Aldosterone Concentration ◽

Control Value ◽

Renal Vascular

The present study was designed to examine the acute and chronic effects of increased levels of circulating bradykinin (BK) on control of renal hemodynamics, electrolyte excretion, and arterial pressure. Intrarenal infusion of BK (50 ng X kg-1 X min-1) for 60 min in five anesthetized dogs with renal perfusion pressure maintained at a constant level of 108 +/- 1 mmHg had no significant effect on glomerular filtration rate (GFR), whereas it increased renal blood flow (RBF) from a control value of 230 +/- 14 to 282 +/- 18, 266 +/- 15, and 253 +/- 17 ml/min after 15, 30, and 60 min of infusion, respectively. Acute intrarenal infusion of BK also increased urine volume (UV) from 0.255 +/- 0.044 to 0.523 +/- 0.103 ml/min and urinary sodium excretion (UNaV) from 5.72 +/- 1.5 to 13.7 +/- 3.4 mueq/min. To determine whether the potent acute effects of BK on RBF, UV, and UNaV lead to a chronic reduction in arterial pressure, BK (50 ng X kg-1 X min-1) was infused intrarenally for 7 days in conscious dogs. Intrarenal infusion of BK for 7 days had no significant effect on GFR, UNaV, UV, or arterial pressure. However, BK elevated renal plasma flow and decreased renal vascular resistance throughout the 7 days of infusion. Chronic intrarenal BK infusion caused no significant changes in plasma renin activity or plasma aldosterone concentration. Results from these studies indicate that although increased levels of bradykinin in the renal circulation can have potent acute effects on RBF, UV, and UNaV, these effects on UV and UNaV are not sustained and therefore do not result in long-term changes in arterial pressure.

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Evidence that intrarenal bradykinin plays a role in regulation of renal function

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1993.265.4.e648 ◽

1993 ◽

Vol 265 (4) ◽

pp. E648-E654 ◽

Cited By ~ 5

Author(s):

H. M. Siragy

Keyword(s):

Renal Function ◽

Sodium Excretion ◽

Sodium Intake ◽

Renal Plasma Flow ◽

Plasma Renin ◽

Urinary Sodium Excretion ◽

Sodium Balance ◽

Kinin System ◽

Plasma Aldosterone Concentration ◽

Low Sodium

Bradykinin (BK) is produced by the kidney, but the role of the renal kallikrein-kinin system (KKS) in the control of renal function is not understood. We studied the effects of intrarenal infusion of the BK antagonist, D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg-trifluoroacetic acid (BKA, n = 5) and BK (n = 4) alone or combined with antagonist (BKA 0.025 ng.kg-1 x min-1 + BK 0.25 ng.kg-1 x min-1, n = 4) in uninephrectomized conscious dogs in sodium balance at 10 and 80 meq/day. During low sodium intake, administration of BKA (infusions from 0.025 to 2.5 ng.kg-1 x min-1) caused a significant antidiuresis (P < 0.0001) and antinatriuresis (P < 0.0001) and a decrease in fractional sodium excretion (P < 0.0001). There were no changes in estimated renal plasma flow (RPF) or glomerular filtration rate during intrarenal administration of BKA at 0.025 and 0.25 ng.kg-1 x min-1. A dose of 2.5 ng.kg-1 x min-1 BKA caused a significant decrease in RPF. There were no changes in plasma aldosterone concentration, plasma renin activity, or systemic arterial pressure during intrarenal BKA administration. At 80 meq/day sodium balance (n = 5), intrarenal administration of BKA did not cause any systemic or renal effects. Intrarenal administration of BK at 0.25 ng.kg-1 x min-1 during low sodium balance caused an increase in urine flow rate and urinary sodium excretion. Coinfusion of BK with BKA completely abrogated the renal excretory changes induced by BKA. These data suggest that intrarenal KKS plays a role in control of renal function largely by a tubular mechanism during low sodium intake.

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A Comparison of the Renal and Neuroendocrine Effects of Two 5-Hydroxytryptamine Renal Prodrugs in Normal Man

Clinical Science ◽

10.1042/cs0850607 ◽

1993 ◽

Vol 85 (5) ◽

pp. 607-614 ◽

Cited By ~ 16

Author(s):

T. C. Li Kam Wa ◽

S. Freestone ◽

R. R. Samson ◽

N. R. Johnson ◽

M. R. Lee

Keyword(s):

Renal Plasma Flow ◽

Plasma Renin ◽

Urinary Sodium Excretion ◽

Serum Growth Hormone ◽

Plasma Aldosterone Concentration ◽

Urinary Dopamine ◽

Normal Man ◽

Male Subjects ◽

Placebo Infusion ◽

Observation Period

1. The effects of 1 h intravenous infusions of equimolar amounts (45 nmol min−1 kg−1) of two putative 5-hydroxytryptamine renal prodrugs, 5-hydroxy-L-tryptophan and γ-L-glutamyl-5-hydroxy-L-tryptophan, were investigated in a randomized, placebo-controlled, cross-over study in nine healthy male subjects. 2. Cumulative urinary 5-hydroxytryptamine excretion over the 3 h observation period rose by about 370-fold after 5-hydroxy-L-tryptophan and 390-fold after γ-L-glutamyl-5-hydroxy-L-tryptophan when compared with placebo infusion. Urinary 5-hydroxy-L-tryptophan excretion was three times higher after administration of γ-L-glutamyl-5-hydroxy-L-tryptophan than after 5-hydroxy-L-tryptophan infusion. Urinary 5-hydroxyindole-3-acetic acid excretion after 5-hydroxy-L-tryptophan infusion was significantly greater than that after γ-L-glutamyl-5-hydroxy-L-tryptophan administration. Urinary dopamine excretion was not affected by either compound when compared with placebo. 3. 5-Hydroxy-L-tryptophan significantly reduced urine flow rate and urinary sodium excretion. γ-L-Glutamyl-5-hydroxy-L-tryptophan was antinatriuretic but did not affect urine output. These changes occurred without significant alterations in effective renal plasma flow and glomerular filtration rate. 4. Both 5-hydroxy-L-tryptophan and γ-L-glutamyl-5-hydroxy-L-tryptophan significantly increased plasma aldosterone concentration without a concomitant rise in plasma renin activity. The increase after γ-L-glutamyl-5-hydroxy-L-tryptophan was smaller and delayed. 5-Hydroxy-L-tryptophan, but not γ-glutamyl-5-hydroxy-L-tryptophan, increased serum growth hormone concentration. 5. There was a significant increase in diastolic blood pressure after 5-hydroxy-L-tryptophan administration, but not after γ-L-glutamyl-5-hydroxy-L-rryptophan. 6. These results show that both prodrugs generate 5-hydroxytryptamine. The antinatriuresis after both compounds is presumably mediated by intrarenally generated 5-hydroxytryptamine and this appears to be predominantly a tubular effect. The urinary metabolite data and greater extrarenal effects produced by 5-hydroxy-L-tryptophan indicate that the glutamyl derivative is relatively more selective for the kidney than 5-hydroxy-L-tryptophan.

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Angiotensin II and Not Sodium Status is the Major Determinant of the Agonistic/Antagonistic Balance of Saralasin's Actions

Clinical Science ◽

10.1042/cs059075s ◽

1980 ◽

Vol 59 (s6) ◽

pp. 75s-78s ◽

Cited By ~ 3

Author(s):

R. Fagard ◽

A. Amery ◽

P. Lijnen

Keyword(s):

Angiotensin Ii ◽

Sodium Excretion ◽

Sodium Intake ◽

Plasma Renin ◽

Urinary Sodium Excretion ◽

Urinary Sodium ◽

Plasma Angiotensin ◽

Group 3 ◽

Group 2 ◽

Group 1

1. To study which factors determine the balance between the antagonistic and agonistic effects of the angiotensin II analogue [Sar1,Ala8]-angiotensin II (saralasin) in man, saralasin was infused in subjects on a ‘normal’ sodium intake (group 1) during sodium restriction with appropriately elevated plasma angiotensin II levels (group 2) and in sodium-restricted subjects in whom plasma angiotensin II was suppressed by converting enzyme inhibition with captopril (group 3). 2. The action of saralasin was agonistic in group 3, antagonistic in group 2 and variable in group 1. 3. For groups 1 and 2 together the saralasin-induced changes of arterial pressure, of plasma aldosterone and of plasma renin were significantly related to control plasma angiotensin II but also to the 24 h urinary sodium excretion. When group 3 was included the changes remained significantly related to plasma angiotensin II but not to the urinary sodium excretion. 4. The results indicate that angiotensin II and not sodium status determines the agonistic/antagonistic balance of saralasin's actions.

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Dissociation of dipsogenic and pressor responses to chronic central angiotensin II in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1982.242.5.r498 ◽

1982 ◽

Vol 242 (5) ◽

pp. R498-R504 ◽

Cited By ~ 1

Author(s):

R. Di Nicolantonio ◽

F. A. Mendelsohn ◽

J. S. Hutchinson ◽

Y. Takata ◽

A. E. Doyle

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Plasma Renin Activity ◽

Sodium Excretion ◽

Plasma Renin ◽

Urinary Sodium Excretion ◽

Systemic Circulation ◽

Ang Ii ◽

Pressor Responses ◽

Maximal Rise

Chronic intracerebroventricular (icv) infusion of angiotensin II (ANG II) (6 micrograms/h) in rats resulted in a sustained 70-mmHg rise in blood pressure during 7 days of treatment. A marked dipsogenic response preceded the maximal rise in blood pressure, peaked at 24 h, and returned to control by the 5th day. Urinary sodium excretion rose on the 1st day of infusion but thereafter was not different from that of vehicle-infused rats. ANG II-infused rats showed a small but significant kaliuresis, a fall in serum osmolality (5.5 mosmol/kg), but no change in plasma Na+, K+, or glucose. Rats infused with the same dose of ANG II intravenously showed a small, 8-mmHg rise in blood pressure, but none of the changes noted after icv ANG II. Plasma renin activity was suppressed in rats infused with ANG II by both routes. We conclude that the pressor, dipsogenic, and renal excretory effects of icv ANG II are mediated centrally and cannot be explained by leakage of the peptide into the systemic circulation. Furthermore, the pressor and dipsogenic effects of ANG II become clearly dissociated during chronic icv infusion.

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The Influence of Potassium on the Renal Vasculature and the Adrenal Gland, and Their Responsiveness to Angiotensin II in Normal Man

Clinical Science ◽

10.1042/cs0490527 ◽

1975 ◽

Vol 49 (6) ◽

pp. 527-534 ◽

Cited By ~ 14

Author(s):

N. K. Hollenberg ◽

G. Williams ◽

B. Burger ◽

I. Hooshmand

Keyword(s):

Blood Flow ◽

Angiotensin Ii ◽

Plasma Renin Activity ◽

Renal Blood Flow ◽

Plasma Renin ◽

Renin Activity ◽

Renal Vasculature ◽

Plasma Aldosterone Concentration ◽

Potassium Intake ◽

Normal Man

1. The effect of modifying potassium intake on arterial plasma renin activity, angiotensin II and aldosterone concentrations, renal blood flow and their responses to exogenous angiotensin II has been assessed in twenty-six normal subjects. 2. Reduced potassium intake was associated with a significant increase in circulating renin activity and angiotensin II concentration and a significant reduction in renal blood flow. Conversely, a high potassium intake was associated with a significant increase in plasma aldosterone concentration and renal blood flow without alteration in plasma renin activity or angiotensin II concentration. 3. Reduced potassium intake decreased both the renal vascular and the adrenal response to infused angiotensin II. Conversely, an increased potassium intake enhanced the responsiveness of both systems. 4. The results suggest an important influence of potassium-induced renin-angiotensin system responses on both the renal vasculature and adrenal glomerulosa cell in normal man.

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The Renin-Aldosterone System in Exaggerated Natriuresis of Essential Hypertension

Clinical Science ◽

10.1042/cs0530573 ◽

1977 ◽

Vol 53 (6) ◽

pp. 573-578 ◽

Cited By ~ 1

Author(s):

E. B. Pedersen ◽

H. J. Kornerup

Keyword(s):

Blood Pressure ◽

Essential Hypertension ◽

Sodium Excretion ◽

Plasma Renin ◽

Urinary Sodium Excretion ◽

Plasma Aldosterone ◽

Urinary Sodium ◽

Mean Blood Pressure ◽

Plasma Aldosterone Concentration ◽

Plasma Renin Concentration

1. The effect of intravenous loading with 500 ml of sodium chloride solution (50 g/l) on plasma renin concentration, plasma aldosterone concentration, urinary sodium excretion and mean blood pressure was studied in 15 young patients with mild essential hypertension and 10 healthy normotensive control subjects. 2. Plasma renin concentration and plasma aldosterone concentration were suppressed to the same degree during loading in both the hypertensive and normotensive groups. Urinary sodium excretion was significantly higher in the hypertensive patients than in the normotensive subjects. Mean blood pressure increased slightly in both groups. 3. Plasma renin concentration and plasma aldosterone concentration were significantly correlated in both groups before sodium loading. The increase in urinary sodium excretion was significantly correlated to the suppression of plasma aldosterone concentration in the hypertensive, but not in the normotensive, group. No correlation was found between changes in urinary sodium excretion and changes in plasma renin concentration or mean blood pressure. 4. The results indicate that the suppressibility of the renin—aldosterone system by hyperosmotic sodium chloride solution is normal in young patients with mild essential hypertension. It is suggested that the changes in plasma aldosterone concentration induced by sodium loading might be involved in the regulation of exaggerated natriuresis in essential hypertension.

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Intrarenal DA2 dopamine receptor stimulation in the conscious dog

AJP Renal Physiology ◽

10.1152/ajprenal.1992.262.6.f932 ◽

1992 ◽

Vol 262 (6) ◽

pp. F932-F938 ◽

Cited By ~ 4

Author(s):

H. M. Siragy ◽

R. A. Felder ◽

M. J. Peach ◽

R. M. Carey

Keyword(s):

Renal Function ◽

Dopamine Receptors ◽

Sodium Excretion ◽

Sodium Intake ◽

Plasma Renin ◽

Urinary Sodium Excretion ◽

Receptor Stimulation ◽

Plasma Aldosterone Concentration ◽

Ly 171555 ◽

Renal Dopamine

DA2 dopamine receptors are present in renal blood vessels and glomeruli. Stimulation of DA1 dopamine receptors leads to renal vasodilation, diuresis, and natriuresis, but a functional role for renal DA2 receptors is largely unknown. We investigated the possible role of DA2 receptors in the control of renal function by intrarenal infusion of a highly specific DA2 agonist, LY 171555 (LY), in conscious uninephrectomized dogs (n = 5) in metabolic balance at sodium intake of 40 meq/day. The infusion of LY at 0.5 pmol.kg-1.min-1 did not change the urinary sodium excretion or renal hemodynamic function. A significant dose-dependent antidiuresis (F = 8.1, P less than 0.0001) and antinatriuresis (F = 93.3, P less than 0.0001) and a decrease in filtration fraction (F = 2.3, P less than 0.02) occurred as the LY dose was increased from 1.0 to 10.0 pmol.kg-1.min-1. There were no changes in systemic plasma renin activity, plasma aldosterone concentration, or mean arterial pressure during intrarenal LY administration. These data suggest that intrarenal DA2 receptor stimulation with LY decreases renal sodium excretion in part by hemodynamic mechanisms. Renal dopamine may act at vascular and/or glomerular DA2 receptors to modulate renal function.

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Effects of hypoproteinemia on renal hemodynamics, arterial pressure, and fluid volume

AJP Renal Physiology ◽

10.1152/ajprenal.1987.252.1.f91 ◽

1987 ◽

Vol 252 (1) ◽

pp. F91-F98

Author(s):

R. D. Manning

Keyword(s):

Mean Arterial Pressure ◽

Arterial Pressure ◽

Sodium Excretion ◽

Sodium Intake ◽

Renal Plasma Flow ◽

Urinary Sodium Excretion ◽

Renal Hemodynamics ◽

Fluid Volume ◽

Urinary Sodium ◽

Plasma Aldosterone Concentration

The effects of long-term hypoproteinemia on renal hemodynamics, arterial pressure, and fluid volume were studied in eight conscious dogs over a 34-day period. Plasma protein concentration (PPC) was decreased by daily plasmapheresis, and the effects of decreasing and increasing sodium intake were measured. By the 12th day of plasmapheresis, during which sodium intake was 30 meq/day, PPC had decreased to 2.5 g/dl from a control value of 7.2 g/dl, mean arterial pressure had decreased to 78% of control, glomerular filtration rate (GFR) was 75.2% of control, and urinary sodium excretion was decreased. By day 18 of plasmapheresis, estimated renal plasma flow (ERPF) was decreased to 60% of control due to the decreased arterial pressure and an increase in renal vascular resistance. Also, plasma renin activity and plasma aldosterone concentration were both increased, and the relationship between mean arterial pressure and urinary sodium excretion was distinctly shifted to the left along the arterial pressure axis. In contradistinction to acute experiments, chronic hypoproteinemia results in decreases in GFR, ERPF, and urinary sodium excretion and has marked effects on both fluid volume and arterial pressure regulation.

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