Effect of inhibition of MAO and COMT on intrarenal dopamine and serotonin and on renal function

2001 ◽  
Vol 280 (1) ◽  
pp. R248-R254 ◽  
Author(s):  
Yongqing Wang ◽  
Theresa J. Berndt ◽  
Jennifer M. Gross ◽  
Michael A. Peterson ◽  
Mathew J. So ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Monoamine Oxidase ◽  
Filtration Rate ◽  
Interstitial Fluid ◽  
Fractional Excretion ◽  
Urine Flow ◽  
Arterial Blood ◽  
Fractional Excretion Of Sodium

The purpose of the present investigation was to study the effects of inhibition of monoamine oxidase (MAO) and/or catechol- O-methyltransferase (COMT), enzymes involved in the degradation of dopamine (DA) and serotonin (5-HT), on intrarenal DA and 5-HT, as reflected in the renal interstitial fluid (RIF) microdialysate and urine, and on renal function. Inhibition of MAO selectively increased RIF 5-HT from 3.16 ± 0.38 to 8.03 ± 1.83 pg/min ( n = 7, P < 0.05), concomitant with decreases in mean arterial blood pressure and glomerular filtration rate (2.09 ± 0.18 to 1.57 ± 0.22 ml/min, n = 7, P < 0.05). Inhibition of COMT significantly increased RIF DA (3.47 ± 0.70 to 8.68 ± 1.96 pg/min, n = 9, P < 0.05), urinary DA (2.00 ± 0.16 to 2.76 ± 0.26 ng/min, n = 9, P < 0.05), and absolute excretion of sodium (6.42 ± 2.00 to 9.82 ± 1.62 μmol/min, n = 10, P < 0.05). Combined inhibition of MAO and COMT significantly increased RIF DA, urinary DA, and urinary 5-HT, which was accompanied with increases in urine flow rate, and absolute (3.03 ± 0.59 to 8.40 ± 1.61 μmol/min, n = 9, P < 0.01) and fractional excretion of sodium. We conclude that inhibition of MAO selectively increases RIF 5-HT. COMT appears to be more important than MAO in the metabolism of intrarenal DA. Physiological increases in intrarenal DA/5-HT induced by inhibition of their degrading enzymes are accompanied with significant alterations of renal function.

Supersensitivity to norepinephrine in chronically denervated kidneys: evidence for a postsynaptic effect

1987 ◽  
Vol 65 (11) ◽  
pp. 2219-2224 ◽  
Author(s):  
J. Krayacich ◽  
R. L. Kline ◽  
P. F. Mercer
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Fractional Excretion ◽  
Urine Flow ◽  
Fractional Excretion Of Sodium ◽  
Infusion Of Norepinephrine

Denervation supersensitivity in chronically denervated kidneys increases renal responsiveness to increased plasma levels of norepinephrine. To determine whether this effect is caused by presynaptic (i.e., loss of uptake) or postsynaptic changes, we studied the effect of continuous infusion of norepinephrine (330 ng/min, i.v.) and methoxamine (4 μg/min, i.v.), an α1 adrenergic agonist that is not taken up by nerve terminals, on renal function of innervated and denervated kidneys. Ganglionic blockade was used to eliminate reflex adjustments in the innervated kidney and mean arterial pressure was maintained at preganglionic blockade levels by an infusion of arginine vasopressin. With renal perfusion pressure controlled there was a significantly greater decrease in renal blood flow (−67 ± 9 vs. −33 ± 8%), glomerular filtration rate (−60 ± 9 vs. −7 ± 20%), urine flow (−61 ± 7 vs. −24 ± 11%), sodium excretion (−51 ± 15 vs. −32 ± 21%), and fractional excretion of sodium (−50 ± 9 vs. −25 ± 15%) from the denervated kidneys compared with the innervated kidneys during the infusion of norepinephrine. During the infusion of methoxamine there was a significantly greater decrease from the denervated compared with the innervated kidneys in renal blood flow (−54 ± 10 vs. −30 ± 14%), glomerular filtration rate (−51 ± 11 vs. −19 ± 17%), urine flow (−55 ± 10 vs. −39 ± 10%), sodium excretion (−70 ± 9 vs. −59 ± 11%), and fractional excretion of sodium (−53 ± 10 vs. −41 ± 10%). These results suggest that vascular and tubular supersensitivity to norepinephrine in chronically denervated kidneys is due to postsynaptic changes involving α1-adrenergic receptors.

Endothelin-induced natriuresis and diuresis are pressure-dependent events in the rat

1993 ◽  
Vol 265 (1) ◽  
pp. R90-R96 ◽  
Author(s):  
K. Uzuner ◽  
R. O. Banks
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Arterial Pressure ◽  
Filtration Rate ◽  
Urine Flow ◽  
Female Rats ◽  
Arterial Blood ◽  
Site Of Action ◽  
Baseline Values ◽  
The Right

The goal of the current study was to determine the mechanism by which doses of endothelin (ET) that do not markedly affect the glomerular filtration rate (GFR) cause a natriuresis and diuresis. ET was infused into pentobarbital-anesthetized female rats at 50 ng.kg-1.min-1 iv for 30 min. In controls (n = 6 rats; n = 5 in all other groups), ET increased mean arterial blood pressure (MAP) from 95 +/- 2 to 131 +/- 2 (SE) mmHg, Na excretion (UNa V) from 0.34 +/- 0.07 to 1.83 +/- 0.2 meq/min, and urine flow rate (V) from 13 +/- 1 to 24 +/- 3 ml/min (all P < 0.01 vs. baseline). At 15 min during infusion of ET, the GFR was not affected (2.1 +/- 0.1 to 2.2 +/- 0.1 ml/min) but modestly decreased to 1.8 +/- 0.1 ml/min at 30 min (P < 0.05 vs. baseline). Either removing the capsule from both kidneys during surgery or maintaining renal arterial pressure at baseline values with an adjustable clamp on the aorta above the right renal artery abolished the ET-induced increase in UNa V and V. Meclofenamate also did not alter the ET-induced increase in MAP, V, or UNa V. To determine the intrarenal site of action of ET, experiments were conducted with ET plus amiloride or with a combination of amiloride plus furosemide; there was a larger ET-induced diuresis and natriuresis in amiloride-treated rats and an even larger response with amiloride plus furosemide compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-(1–7) in the ovine fetus

2001 ◽  
Vol 280 (2) ◽  
pp. R404-R409 ◽  
Author(s):  
Karen M. Moritz ◽  
Duncan J. Campbell ◽  
E. Marelyn Wintour
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Flow Rate ◽  
Filtration Rate ◽  
Plasma Concentrations ◽  
Urine Flow ◽  
Urine Flow Rate ◽  
Ang Ii ◽  
Arterial Blood

In the adult animal, ANG-(1–7) may counterbalance some effects of ANG II. Its effects in the fetus are unknown. Basal ANG-(1–7), ANG I, ANG II, and renin concentrations were measured in plasma from ovine fetuses and their mothers ( n = 10) at 111 days of gestation. In the fetus, concentrations of ANG I, ANG-(1–7), and ANG II were 86 ± 21, 13 ± 2, and 14 ± 2 fmol/ml, respectively. In the ewe, concentrations of ANG I were significantly lower (20 ± 4 fmol/ml, P < 0.05) as were concentrations of ANG-(1–7) (2.9 ± 0.6 fmol/ml), whereas ANG II concentrations were not different (10 ± 1 fmol/ml). Plasma renin concentrations were higher in the fetus (4.8 ± 1.1 pmol ANG I · ml−1 · h−1) than in the ewe (0.9 ± 0.2 pmol · ml−1 · h−1, P < 0.05). Infusion of ANG-(1–7) (∼9 μg/h) for a 3-day period caused a significant increase in plasma concentrations of ANG-(1–7) reaching a maximum of 448 ± 146 fmol/ml on day 3 of infusion. Plasma levels of ANG I and II as well as renin were unchanged by the infusion. Urine flow rate, glomerular filtration rate, and fetal arterial blood pressure did not change and were not different than values in fetuses receiving a saline infusion for 3 days ( n = 5). However, the osmolality of amniotic and allantoic fluid was significantly higher in fetuses that received ANG-(1–7). Also, compared with the saline-infused animals, mRNA expression levels of renin, the AT1 receptor, and AT2 receptor were elevated in kidneys of fetuses that received infusions of ANG-(1–7). Infusion of an ANG-(1–7) antagonist {[d-Ala7]-ANG-(1–7), 20 μg/h} for 3 days had no effect on fetal blood pressure or renal function. In conclusion, although infusion of ANG-(1–7) did not affect fetal urine flow rate, glomerular filtration rate, or blood pressure, changes in fetal fluids and gene expression indicate that ANG-(1–7) may play a role in the fetal kidney.

Kidney cross transplants in Dahl salt-sensitive and salt-resistant rats

1992 ◽  
Vol 262 (6) ◽  
pp. H1809-H1817 ◽  
Author(s):  
P. C. Churchill ◽  
M. C. Churchill ◽  
A. K. Bidani
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Fractional Excretion ◽  
Transplanted Kidney ◽  
Native Kidney ◽  
Clearance Studies ◽  
Genetically Determined

Previous kidney cross-transplant studies have demonstrated that the genotype of the kidney plays a role in determining the blood pressure of the recipient in Dahl salt-sensitive (S) and salt-resistant (R) rats. The present studies were designed to elucidate this role. Kidney cross transplants were performed in unilaterally nephrectomized male recipients (John Rapp strains), such that each rat had a native kidney and a transplanted kidney of the opposite genotype. S and R rats with a native kidney and a transplanted kidney of the same genotype served as controls. After 4 wk on a 7.8% NaCl diet, rats were anesthetized and renal clearance studies were performed. S kidneys had lower glomerular filtration rate (GFR) and renal plasma flow (RPF) than R kidneys, and these differences were determined by the kidney's genotype rather than the recipient's, since S kidneys in R recipients tended to have lower GFR and RPF than R kidneys in S recipients. In contrast, independent of the kidney's genotype, the kidneys in S rats tended to have higher fractional excretion of H2O and Na (FEH2O and FENa) than the kidneys in R rats. Thus there were genetically determined differences in renal function between S and R rats; some (RPF and GFR) were intrinsic to the kidney, whereas others (FEH2O and FENa) were intrinsic to the host.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of vasopressin and oxytocin on glomerular filtration rate in the conscious rat: contribution to the natriuretic response

1994 ◽  
Vol 141 (1) ◽  
pp. 59-67 ◽  
Author(s):  
M L Forsling ◽  
J M Judah ◽  
R J Windle
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Plasma Concentrations ◽  
Fractional Excretion ◽  
Conscious Rat ◽  
Arterial Blood ◽  
Fractional Excretion Of Sodium ◽  
Dose Dependent ◽  
Higher Doses

Abstract Urine flow, sodium excretion, mean arterial blood pressure and glomerular filtration rate (GFR) were detennined in the conscious unrestrained rat infused with hypotonic saline. The effects of vasopressin infused at 24 and 160 pmol/min and oxytocin infused at 30 and 200 pmol/min were determined. The lower doses of each hormone gave plasma concentrations within the physiological range whereas the higher doses produced plasma concentrations equivalent to those seen following dehydration. Vasopressin produced dose-dependent antidiuretic and natriuretic responses. Hormone infused at both rates increased the clearance of sodium, but only the higher dose caused a significant increase in GFR. Fractional excretion of sodium was significantly elevated by both doses. Oxytocin produced dose-dependent diuretic and natriuretic responses. Again both rates of infusion increased the clearance of sodium, but only the higher dose caused a significant increase in GFR. The lower dose caused a significant increase in the fractional excretion of sodium. It appears, therefore, that increases in GFR may have a role in the natriuretic response to both hormones. However, this response can also be seen when GFR remains unchanged. This fact, together with the observed increases in the fractional excretion of sodium, indicates that these hormones have additional tubular actions. Journal of Endocrinology (1994) 141, 59–67

Amiloride-sensitive lithium reabsorption during doxazosin-induced blood pressure reduction in rats

1991 ◽  
Vol 81 (6) ◽  
pp. 809-814 ◽  
Author(s):  
Jørgen Søberg Petersen ◽  
Michael Shalmi ◽  
Martin Bak ◽  
Niels Lomholt ◽  
Sten Christensen
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Mean Arterial Blood Pressure ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Excretion Rate ◽  
Urine Flow ◽  
Lithium Clearance ◽  
Arterial Blood

1. The effects of acute systemic α1-anoceptor blockade by doxazosin on glomerular filtration rate, urine flow, sodium clearance and lithium clearance were investigated in acutely prepared conscious rats. 2. Clearance experiments were performed during water diuresis (20 mmol/l NaCl and 110 mmol/l glucose, 3 ml/h). After a control period, animals were randomized to one of the following treatments: time-control (n = 9), doxazosin (50 μg primer; 30 μg h−1 kg−1) (n = 10), amiloride (1 mg primer; 2.4 mg h−1 kg−1) (n = 10) and doxazosin plus amiloride (n = 9). 3. Doxazosin reduced the mean arterial blood pressure from 125 to 108 mmHg; this was associated with transient reductions in glomerular filtration rate, urine flow and lithium clearance. After the transient anti-diuresis, the sodium excretion rate remained reduced in doxazosin-infused animals. Amiloride increased the sodium excretion rate without having effects on other variables. When doxazosin was given together with amiloride, the reduction in lithium clearance observed during the transient reduction in glomerular filtration rate and urine flow, was partly abolished. Thus the fractional lithium excretion was transiently increased in rats given doxazosin plus amiloride (from 29 to 40%), whereas in rats given doxazosin alone a non-significant reduction was observed (from 28 to 25%). The dissociation between lithium clearance and fractional lithium excretion in the two doxazosin-infused groups was only significant during the transient reduction in glomerular filtration rate and urine flow. 4. The results provide evidence for an amiloride-sensitive lithium reabsorption during acute systemic α1-adrenoceptor blockade. It is suggested that activation of baroreflexes during the acute reduction in mean arterial blood pressure is responsible for stimulation of distal lithium reabsorption by an unknown mechanism.

Meclofenamate and urine concentration with and without exposure of the renal papilla

1981 ◽  
Vol 240 (5) ◽  
pp. F423-F429 ◽  
Author(s):  
R. J. Roman ◽  
C. Lechene
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Urine Osmolality ◽  
Urine Concentration ◽  
Prostaglandin Synthesis ◽  
Urine Flow ◽  
Renal Papilla ◽  
Arterial Blood ◽  
Pelvic Urine

The recent finding that inhibitors of prostaglandin synthesis prevent the fall in urine concentration produced by papillary exposure challenges the hypothesis that contact between the pelvic urine and papilla is essential to the renal concentrating process. The present study examines the change in urine osmolality produced by exposure of the renal papilla in rats given meclofenamate. In control animals urine osmolality(Uosmol) decreased 57% after 2 h of exposure of the renal papilla. In rats given meclofenamate 4 mg/kg urine osmolality increased 16%, urine flow decreased 30%, and glomerular filtration rate was unchanged in the nonexposed kidney. Meclofenamate, however, did not alter the decrease in Uosmol seen in the kidney with the exposed papilla. Meclofenamate 10 mg/kg was also ineffective in preventing the fall in urine osmolality produced by papillary exposure, although this higher dose decreased glomerular filtration rate and arterial blood pressure. These results are consistent with the finding that pelvic urine urea is important to the urinary concentrating process and with the hypothesis that urine osmolality falls after papillary exposure because contact between pelvic urine and papilla is interrupted.

Intraruminal rehydration of ovine fetuses

1991 ◽  
Vol 261 (6) ◽  
pp. R1381-R1387
Author(s):  
M. G. Ross ◽  
D. J. Sherman ◽  
M. G. Ervin ◽  
L. Day
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Filtration Rate ◽  
Plasma Osmolality ◽  
Urine Osmolality ◽  
Distilled Water ◽  
Intravascular Volume ◽  
Fetal Plasma ◽  
Arterial Blood ◽  
Arterial Po2

During oral rehydration of adult mammals, oropharyngeal stimulation, the act of swallowing, and/or gastric factors contribute to a rapid decrease in plasma arginine vasopressin (AVP) that precedes plasma osmolality changes. To determine whether similar mechanisms are present in the developing fetus, six chronically prepared ovine fetuses were rehydrated with intraruminal (IR) distilled water infusions (1 ml.kg-1.min-1 for 60 min) after 43 +/- 3 h of maternal water deprivation. In response to maternal dehydration, significant increases were noted in maternal and fetal mean plasma osmolalities, sodium and AVP concentrations, and fetal urine osmolality. As estimated by hematocrit, fetal intravascular volume decreased by 11%. Fetal rehydration via IR distilled water infusion evoked a significant decrease in fetal plasma osmolality but no change in urine osmolality. Unexpectedly, fetal arterial blood pressure increased and arterial PO2 decreased while fetal hematocrit indicated a further 7% decrease in intravascular volume after the IR infusion. There was a nonsignificant trend toward increased fetal glomerular filtration rate, urine volume, and plasma AVP concentrations. Identical IR water infusions to five euhydrated fetuses resulted in significant decreases in fetal plasma osmolality and increases in glomerular filtration rate, urine flow, and osmolar excretion. The euhydrated fetuses also exhibited significant increases in mean arterial blood pressure and hematocrit and decreased fetal arterial PO2. These results indicate that IR water does not suppress AVP secretion in the dehydrated ovine fetus. Rather, both euhydrated and dehydrated fetuses exhibit an idiosyncratic vasoconstrictive response to IR water.

Renal actions of endothelin: interaction with prostacyclin

1990 ◽  
Vol 259 (4) ◽  
pp. F645-F652 ◽  
Author(s):  
S. Y. Chou ◽  
A. Dahhan ◽  
J. G. Porush
Keyword(s):  
Blood Pressure ◽  
Filtration Rate ◽  
Prostaglandin Synthesis ◽  
Urine Flow ◽  
Renin Release ◽  
Arterial Blood ◽  
Anesthetized Dogs ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Arterial Plasma ◽  
Prostacyclin Synthesis

The renal actions of endothelin were examined by infusing it intrarenally in anesthetized dogs at 4 ng.min-1.kg-1 without affecting arterial blood pressure or cardiac output. Endothelin infusion caused a transient and significant increase in renal blood flow (RBF) by 13 +/- 2%, followed by large decreases in RBF and glomerular filtration rate (GFR; by 26 +/- 2 and 23 +/- 7%, respectively) but did not alter urine flow rate or absolute sodium excretion. After endothelin infusion, renal venous and arterial plasma 6-ketoprostaglandin F1 alpha increased from 250 +/- 58 and 117 +/- 31 to 1,044 +/- 249 and 617 +/- 211 pg/ml, respectively, and its renal output increased from 339 +/- 99 to 963 +/- 202 pg.min-1.g-1 (P less than 0.01 for all). The renal prostacyclin synthesis was augmented by endothelin without stimulating the renal renin release or norepinephrine output. Inhibition of prostaglandin synthesis with indomethacin partially prevented the early renal vasodilation induced by endothelin, which then caused a more pronounced decline in RBF and GFR (by 65 +/- 7 and 54 +/- 8%, respectively). With suppression of prostacyclin synthesis, inhibition of renin release by endothelin was observed. Thus the vasoconstrictive effects of endothelin on renal hemodynamics are significantly modified by its ability to enhance production of vasodilators, including prostacyclin.

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