Evidence that dopamine-2 mechanisms control renal function

1990 ◽  
Vol 259 (5) ◽  
pp. F793-F800 ◽  
Author(s):  
H. M. Siragy ◽  
R. A. Felder ◽  
N. L. Howell ◽  
R. L. Chevalier ◽  
M. J. Peach ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Urinary Flow ◽  
Plasma Aldosterone Concentration ◽  
Arterial Blood ◽  
Ly 171555 ◽  
Renal Vascular ◽  
Dose Dependent

Dopamine is synthesized by the kidney, and dopamine-2 (DA2) receptors are present in the renal glomerulus. However, no role for DA2 receptors in the kidney has been defined. We investigated the possible role of DA2 receptors in control of renal function by intrarenal infusion of a highly specific DA2 antagonist YM-09151 (YM), in conscious uninephrectomized dogs (n = 5) in metabolic balance at Na intake 40 meq/day. YM infused at 0.01 pmol.kg-1.min-1 did not cause any changes in urinary flow rate or Na excretion. Administration of YM (infusions from 0.1 to 10.0 pmol.kg-1.min-1) caused a significant dose-dependent diuresis (F = 20.3; P less than 0.001) and natriuresis (F = 35.2; P less than 0.0001) and an increase in glomerular filtration rate (F = 45.4; P less than 0.0001), renal plasma flow (F = 209.3; P less than 0.0001), and filtration fraction (F = 11.2; P less than 0.0001). No significant changes in plasma renin activity, plasma aldosterone concentration, or mean arterial blood pressure occurred with any of the doses of YM infused into the renal artery. Coinfusion of LY-171555, a specific DA2 agonist, at a dose that itself did not affect renal function, completely abrogated the renal hemodynamic and excretory changes induced by YM. The data suggest that dopamine produced intrarenally may act at renal vascular and/or glomerular DA2 receptors to control renal function.

Intrarenal renin inhibition increases renal function by an angiotensin II-dependent mechanism

1988 ◽  
Vol 255 (4) ◽  
pp. F749-F754 ◽  
Author(s):  
H. M. Siragy ◽  
N. E. Lamb ◽  
C. E. Rose ◽  
M. J. Peach ◽  
R. M. Carey
Keyword(s):  
Renal Function ◽  
Angiotensin Ii ◽  
Sodium Intake ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Competitive Inhibitor ◽  
Urinary Flow ◽  
Renin Substrate ◽  
Plasma Aldosterone Concentration ◽  
Renin Inhibition

ACRIP is a competitive inhibitor of renin in which an analogue of statine, (3R,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, is incorporated into analogues of porcine renin substrate. ACRIP inhibits the enzymatic activity of renin, thus blocking the initiation of the angiotensin cascade. We studied the intrarenal action of ACRIP in small quantities without measurable systemic effects on renal function. In the first experiment, ACRIP was administered intrarenally at 0.02, 0.2, and 2 micrograms.kg-1.min-1 to uninephrectomized conscious dogs (n = 6) in metabolic balance at sodium intake of 10 meq/day. ACRIP, in doses of 0.02 and 0.2 micrograms.kg-1.min-1, markedly increased urine sodium excretion (UNaV) from 5.8 +/- 1.4 to 15.1 +/- 5.1 and 19.9 +/- 3.2 mu eq/min, respectively. Urinary flow rate (UV) underwent a similar increase and glomerular filtration rate (GFR) increased from 25.7 +/- 2.5 to 35.6 +/- 2.5 at 0.02 micrograms.kg-1.min-1 of ACRIP. Renal plasma flow (RPF), plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were not affected. At 2 micrograms.kg-1.min-1, ACRIP traversed the kidney in quantities large enough to produce a reduction in systemic PRA and mean arterial pressure and caused natriuresis, diuresis, and increased GFR. In a second experiment, ACRIP was administered intrarenally at 0.2 micrograms.kg-1.min-1 in a separate group (n = 4) under identical conditions. ACRIP-induced increases in UV and UNaV were completely blocked by concurrent intrarenal administration of angiotensin II. The results indicate that intrarenal angiotensin II acts as a physiological regulator of renal sodium and fluid homeostasis.

Evidence that intrarenal dopamine acts as a paracrine substance at the renal tubule

1989 ◽  
Vol 257 (3) ◽  
pp. F469-F477 ◽  
Author(s):  
H. M. Siragy ◽  
R. A. Felder ◽  
N. L. Howell ◽  
R. L. Chevalier ◽  
M. J. Peach ◽  
...  
Keyword(s):  
Sodium Excretion ◽  
Sodium Intake ◽  
Renal Plasma Flow ◽  
Sch 23390 ◽  
Plasma Renin ◽  
Systemic Arterial Pressure ◽  
Urinary Flow ◽  
Plasma Aldosterone Concentration ◽  
Renal Dopamine ◽  
Dose Dependent

Dopamine is synthesized within the kidney and dopamine 1 (DA1) receptors are associated with the proximal tubule. In pharmacological doses, dopamine increases renal blood flow and sodium excretion. It is possible that dopamine formed intrarenally acts locally via renal dopamine receptors to control renal function. We investigated the possible paracrine action of renal dopamine by intrarenal administration of a specific DA1 antagonist, Sch 23390, in doses confined to the kidney in conscious uninephrectomized dogs (n = 5) in metabolic balance at a sodium intake of 40 meq/day. Changes (mean +/- SE) in renal excretory and hemodynamic function in response to cumulative infusions of several doses of Sch 23390 (0.01, 0.1, 1.0, 5.0, and 10.0 pmol.kg-1.min-1) were studied. Sch 23390 at 0.01 pmol.kg-1.min-1 did not cause any changes in urinary flow rate or sodium excretion. Sch 23390 in doses from 0.1 to 10.0 mol.kg-1.min-1 caused a significant dose-dependent antidiuresis (F = 44.9, P less than 0.0001) and antinatriuresis (F = 42.1, P less than 0.0001) and a decrease in fractional sodium excretion (F = 44.2, P less than 0.0001). No changes in estimated renal plasma flow, glomerular filtration rate, plasma aldosterone concentration, plasma renin activity, or systemic arterial pressure occurred with any dose of intrarenal Sch 23390 infused into the renal artery. Rebound diuresis and natriuresis occurred after cessation of the DA1 blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

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

1985 ◽  
Vol 248 (1) ◽  
pp. F87-F92 ◽  
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.

Systemic and renal haemodynamic changes in renal schemia/reperfusion injury: impact of erythropoietin

2012 ◽  
Vol 90 (11) ◽  
pp. 1535-1543 ◽  
Author(s):  
Abdel-Aziz M. Hussein ◽  
Nashwa Barakat ◽  
Amira Awadalla ◽  
Ahmed A. Shokeir
Keyword(s):  
Renal Function ◽  
Renal Plasma Flow ◽  
Treated Group ◽  
Significant Rise ◽  
Control Group ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Group I ◽  
Haemodynamic Changes ◽  
Renal Vascular

The objective of this study was to investigate the effects of erythropoietin (EPO) on systemic and renal hemodynamics in a rat model of renal ischemic/reperfusion (I/R) injury. We used 30 male Sprague–Dawley rats distributed among the following 3 groups (10 rats per group): (i) the sham-operated group, (ii) the control group (I/R injury only), and (iii) the EPO-treated group (I/R injury with 1500 U EPO·(kg body mass)–1 on day 0, and 500 U·kg–1 on days 2 and 4 after ischemia). Renal function, arterial blood pressure (ABP), renal plasma flow (RPF), renal blood flow (RBF), and renal vascular resistance (RVR) were measured on days 1, 2, and 7 after ischemia. The expression of endothelial NO synthase (eNOS) and histopathology of kidney were evaluated on day 7. The contractility of aortic strips was recorded from the different groups. The results show that renal function and histopathology were significantly improved after treatment with EPO. Compared with the control group, the EPO-treated group showed a significant increase in RPF, RBF, haematocrite, ABP, eNOS expression, and a decrease in RVR (p < 0.05).The response of aortic strips to the relaxant effect of acetylcholine was improved in the EPO-treated group. In conclusion, treatment with EPO improves renal function and renal haemodynamics in renal I/R injury, and causes significant rise of ABP and haematocrite value.

Systemic hemodynamics and renal function during long-term pathophysiological increases in circulating endothelin

1995 ◽  
Vol 268 (2) ◽  
pp. R375-R381 ◽  
Author(s):  
F. C. Wilkins ◽  
A. Alberola ◽  
H. L. Mizelle ◽  
T. J. Opgenorth ◽  
J. P. Granger
Keyword(s):  
Renal Function ◽  
Renal Plasma Flow ◽  
Peripheral Resistance ◽  
Plasma Renin ◽  
Chronic Hypertension ◽  
Systemic Hemodynamic ◽  
Endothelin 1 ◽  
Control Value ◽  
Renal Vascular

Although recent studies have reported endogenous plasma endothelin levels to be elevated two- to fivefold in chronic pathophysiological states, whether such an increase in circulating endothelin levels alone can lead to significant long-term alterations in cardiovascular and renal function is not known. The purpose of this study was to examine the long-term systemic hemodynamic and renal effects of a pathophysiological increase in plasma endothelin concentration in chronically instrumented, conscious dogs (n = 7). Infusion of endothelin-1 (2.5 ng.kg-1.min-1) for 8 days increased plasma concentration of immunoreactive endothelin approximately two- to threefold from 6.7 +/- 0.4 to 16.0 +/- 2.2 pg/ml. Mean arterial pressure increased 21% from a control value of 86.7 +/- 2.1 to 105.0 +/- 2.5 mmHg during the endothelin infusion period. Cardiac output averaged 2,200 +/- 205 ml/min during control and fell by 33% on day 4 of endothelin infusion (1,484 +/- 146 ml/min) and was still 14% below control after day 8 of endothelin infusion (1,885 +/- 154 ml/min). Endothelin increased total peripheral resistance from 42.0 +/- 3.1 to 80.3 +/- 9.1 mmHg.l-1.min. Increasing plasma endothelin two- to threefold was associated with an increase in renal vascular resistance and decreases in glomerular filtration rate and renal plasma flow. Endothelin-1 had no long-term effect on plasma renin activity or aldosterone concentration. These data indicate the importance of pathophysiological levels of endothelin in controlling renal and cardiovascular function in chronic conditions. Furthermore, the results indicate that endothelin may play a role as a mediator of chronic hypertension in pathophysiological states associated with endothelial dysfunction.

Ontogeny of renal response to specific dopamine DA1-receptor stimulation in sheep

1992 ◽  
Vol 263 (4) ◽  
pp. R868-R873 ◽  
Author(s):  
J. L. Segar ◽  
F. G. Smith ◽  
E. N. Guillery ◽  
P. A. Jose ◽  
J. E. Robillard
Keyword(s):  
Sch 23390 ◽  
Plasma Renin ◽  
Fractional Excretion ◽  
Receptor Activation ◽  
Urinary Flow ◽  
Fetal Sheep ◽  
Plasma Aldosterone Concentration ◽  
Arterial Blood ◽  
Fractional Excretion Of Sodium ◽  
Near Term

The present study was designed to characterize the developmental changes in the renal responses to dopamine DA1-receptor activation in chronically instrumented preterm (109-115 days) and near-term (130-140 days, full term 145 days) fetal sheep. Cumulative doses of the selective DA1-agonist fenoldopam increased mean arterial blood pressure (MABP) in both preterm (+16 +/- 3%) and near-term fetuses (+16 +/- 3%) but had no significant effect on renal blood flow velocity. Infusion of the DA1-antagonist SCH-23390 did not affect the increase in MABP, suggesting that the effect of fenoldopam on MABP was not directly related to activation of DA1-receptors. Fenoldopam infusion had no significant effects on renal function parameters in preterm fetuses. In near-term fetuses, however, fenoldopam increased urinary flow rate (82.6 +/- 20.9%, P < 0.003), glomerular filtration rate (GFR; 16.6 +/- 4.9%, P < 0.01), urinary sodium excretion (40.1 +/- 14.9%, P < 0.02), and fractional excretion of sodium (26.8 +/- 11.2%, P < 0.03). Infusion of the DA1-antagonist SCH-23390 blocked the fenoldopam-induced diuresis and natriuresis but had no significant effect on the rise in GFR. Fenoldopam infusion had no significant effects on plasma renin activity and plasma aldosterone concentration and on urinary prostaglandin (PG) excretion (PGE2, PGF2 alpha, and 6-keto-PGF1 alpha). Taken together, these results suggest that the renal effect of DA1-receptor activation is age dependent and that stimulation of DA1-receptor in near-term fetuses is associated with a diuresis and natriuresis that seem to be independent of renal hemodynamics and adrenal effects.

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

1993 ◽  
Vol 265 (4) ◽  
pp. E648-E654 ◽  
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.

Blood pressure and renal function during chronic changes in sodium intake: role of angiotensin

1980 ◽  
Vol 239 (3) ◽  
pp. F271-F280 ◽  
Author(s):  
J. E. Hall ◽  
A. C. Guyton ◽  
M. J. Smith ◽  
T. G. Coleman
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Sodium Intake ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Plasma Aldosterone ◽  
Filtration Fraction ◽  
Plasma Aldosterone Concentration ◽  
Angiotensin System

The present study was designed to quantitate the role of the renin-angiotensin system (RAS) in determining the chronic relationships between arterial pressure (AP), renal hemodynamics, and Na excretion. In six control dogs, Na balance was achieved during chronic step increases in Na intake from 5 to 500 meq/day with small increases in AP (<7 mmHg), moderate increases in GFR (19%), and decreases in filtration fraction (FF) and plasma renin activity. Similar increases in Na intake in six dogs with angiotensin II (AII) fixed, due to constant intravenous infusion of 5 ng . kg-1 . min-1 AII, caused large increases in AP (42%), GFR (31%) FF, and calculated renal Na reabsorption (TNa) above control. In six dogs with AII formation blocked with SQ 14,225, Na balance at intakes of 5-80 meq/day occurred at reduced AP, GFR, FF, and TNa, although plasma aldosterone concentration (PAC) was not substantially different from that in control dogs. At Na intakes above 240 meq/day, AP was not altered by SQ 14,225. These data indicate that during chronic changes in Na intake the RAS plays a major role, independent of changes in PAC, in allowing Na balance without large changes in GFR or AP. The mechanism whereby AII conserves Na chronically is through increased TNa, since steady-state TNa was increased by AII and decreased by SQ 14,225.

Intrarenal DA2 dopamine receptor stimulation in the conscious dog

1992 ◽  
Vol 262 (6) ◽  
pp. F932-F938 ◽  
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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