Biomedical subjects

M Thonney

Publications and source records attributed to M Thonney.

9 recordsLinked to original sources

PubMed1996

Nitric oxide modulates glomerular filtration and renal blood flow of the newborn rabbit.

The current study was performed in 17 anesthetized and mechanically ventilated newborn rabbits to investigate the role of nitric oxide (NO) in the regulation of basal renal function of the immature kidney. Renal blood flow and glomerular filtration rate were determined by the clearance of p-aminohippuric acid and inulin, respectively. In 9 newborn rabbits (group 1), L-NAME, a NO synthesis inhibitor, significantly increased the renal vascular resistance by 31 +/- 9% and decreased the renal blood flow by 20 +/- 6%. The fraction of filtration significantly increased by 8 +/- 5% despite a delayed decline in glomerular filtration rate by 13 +/- 5%. Mean arterial pressure and heart rate were not altered. In 8 additional newborn rabbits (group 2), L-arginine, the physiological precursor of NO synthesis, partially reversed the renal hemodynamic changes induced by L-NAME. The present results demonstrate that the decrease in NO production induced by L-NAME (1) significantly affects the renal microcirculation of the immature newborn rabbit kidney and (2) predominantly increases the postglomerular renal vascular resistance. Endogenous NO thus appears to play a major role in maintaining the basal perfusion of the immature kidney.

Animals↗

PubMed1996

Role of nitric oxide in the hypoxemia-induced renal dysfunction of the newborn rabbit.

The current study was performed in 30 anesthetized and mechanically ventilated newborn rabbits to investigate the role of the endothelium-derived relaxing factor nitric oxide (NO) in the renal vasoconstriction observed during hypoxemia. Renal blood flow (RBF) and GFR were determined by the clearance of p-aminohippuric acid and inulin, respectively. In nine newborn rabbits (group 1), acute hypoxemia induced a significant decrease in RBF (-17 +/- 7%) and GFR (-11 +/- 6%). A second group of nine animals was used to determine the role of NO in regulating renal hemodynamics of the immature kidney in physiologic conditions. N omega-Nitro-L-arginine methyl ester (L-NAME), a NO synthesis inhibitor, significantly increased the renal vascular resistance by 31 +/- 9% and decreased RBF and GFR (-20 +/- 6% and -13 +/- 5%, respectively). Acute hypoxemia was induced in 12 additional newborn rabbits during L-NAME infusion (group 3) to define the role of NO in the renal vasoconstriction observed during hypoxemia. The changes in renal hemodynamics were greater in this group than in those induced by hypoxemia alone. The present results suggest that: 1) endogenous NO has a crucial role in maintaining basal renal perfusion, 2) the activity of NO synthase is maintained during acute hypoxemia, and 3) NO could blunt the effects of acute hypoxemia in the immature newborn rabbit kidney.

Animals↗

PubMed1995

Comparison of 5-hydroxyindole-acetic acid and para-amino hippurate clearances in newborn rabbits.

Recent study indicates that endogenous 5-hydroxyindole-acetic acid (5-HIAA) clearance can be used as an alternative procedure to para-amino hippurate (PAH) clearance for the estimation of renal plasma flow in human patients. In view of the limitations of PAH clearance measurements in newborn infants we made an attempt to validate the technique of measuring renal blood flow with 5-HIAA quantitatively against PAH clearance. Thirty-four simultaneous determinations of PAH and 5-HIAA clearances were performed in 14 newborn rabbits. 5-HIAA concentrations in plasma and urine were measured by using HPLC coupled with electrochemical detection (Beckman). Renal blood flow was found to range between 0.60 and 6.90 ml/min/kg (mean: 3.39 ml/min/kg) for 5-HIAA and from 0.93 to 6.61 ml/min/kg (mean: 3.68 ml/min/kg) for PAH clearances. There was a significant positive correlation between the values obtained by the two techniques (r = 0.84, P < 0.001). When 5-HIAA clearance was analyzed as a function of plasma 5-HIAA level only a weak, but statistically significant correlation could be detected (r = 0.33, P < 0.05). Plasma 5-HIAA measurement alone, therefore, does not reflect renal blood flow in newborn rabbits. It is concluded that endogenous 5-HIAA clearance might serve as a reliable estimate of renal blood flow in the neonate under different physiologic and pathologic conditions.

Animals↗

PubMed1995

Does endothelin-1 mediate the hypoxemia-induced renal dysfunction in newborn rabbits?

In the newborn rabbit, acute normocapnic hypoxemia increases the renal vascular resistance, leading to renal hypoperfusion and decreased glomerular filtration rate. Endothelin is a potent vasoconstrictor peptide, produced by vascular endothelial cells, which could play a role as a mediator of the hypoxemia-induced renal dysfunction. To test this hypothesis, experiments were performed in 24 anesthetized and mechanically ventilated newborn rabbits. Renal blood flow and glomerular filtration rate were determined by the clearance of p-aminohippuric acid and inulin, respectively. Each animal acted as its own control. In 8 newborn rabbits (group 1), a bolus injection of 5 nmol.kg-1 of endothelin caused a marked increase in mean blood pressure and renal vascular resistance leading to a significant fall in glomerular filtration rate (-12 +/- 4%) and renal blood flow (-16 +/- 3%). A second group of animals (n = 8) confirmed the neutralizing activity of the endothelin-1 antiserum in vivo. In spite of pretreatment with endothelin-1 antiserum, hypoxemia induced an increase in renal vascular resistance (+40 +/- 18%; p < 0.05) associated with a significant fall in glomerular filtration rate (-18 +/- 7%) and renal blood flow (-29 +/- 6%) in 8 newborn rabbits (group 3). The present results suggest that endothelin-1 does not mediate the hypoxemia-induced renal changes.

Animals↗

PubMed1993

Role of endogenous endothelin in renal haemodynamics of newborn rabbits.

Endothelin is a potent vasoconstrictor peptide produced by vascular endothelial cells which could play a role in the physiological regulation of the renal microcirculation. To test this hypothesis, experiments were performed in 24 anaesthetized and mechanically-ventilated newborn rabbits. In 8 newborn rabbits (group 1), a bolus injection of 5 nmol/kg endothelin caused a marked increase in mean blood pressure (MBP) and renal vascular resistance (RVR), leading to a significant fall in glomerular filtration rate (GFR) (by 12% +/- 4%) and renal blood flow (RBF) by 16% +/- 3%). A second group of animals (n = 8) was used for testing the in vivo neutralizing activity of an endothelin-1 antiserum. The antiserum was thereafter infused into 8 additional newborn rabbits (group 3) in order to define the role of endogenous endothelin in modulating the function of the immature kidney. The antiserum induced a surprising increase in RVR (by 34% +/- 9%, P < 0.05) associated with a fall in GFR (by 21% +/- 4%, P < 0.05) and RBF (by 25% +/- 4%, P < 0.05), while the filtration fraction and MBP remained unchanged. The occurrence of a vasoconstrictive response to both high-dose endothelin and to its antiserum could be explained by the recent demonstration that high levels of endothelin lead to renal vasoconstriction, while lower levels induce renal vasodilatation. The present results suggest that endogenous endothelin is active at low levels under normal conditions and that this peptide plays a role in the physiological control of renal function, but not MBP.

Animals↗

PubMed1993

Effects of endothelin on renal function in newborn rabbits.

The renal effects of endothelin-1 were investigated in 16 anesthetized and mechanically ventilated newborn rabbits. Renal blood flow and glomerular filtration rate were determined by the clearance of para-aminohippuric acid and inulin, respectively. Each animal acted as its own control. In eight newborn rabbits, a bolus injection of 5 nmol.kg-1 of endothelin-1 caused an initial fall in mean arterial blood pressure followed by a gradual, significant increase in mean arterial blood pressure that lasted for 45 min. The dramatic increase in renal vascular resistance (+28 +/- 4%) induced by endothelin led to a fall in glomerular filtration rate (-12 +/- 4%) and renal blood flow (-16 +/- 3%). In spite of the reduction of glomerular filtration rate and renal blood flow, urine flow and sodium excretion rates increased significantly (+20 +/- 5% and +49 +/- 9%, respectively). In eight additional newborn rabbits, a bolus injection of 1 nmol.kg-1 of endothelin--a dose that usually induces marked renal and systemic vasoconstriction in adult models--did not affect systemic or renal hemodynamics. In conclusion, endothelin induces renal and systemic vasoconstriction and affects water and sodium homeostasis during the neonatal period. These effects occur under higher doses than those used in adult animals. This age difference in systemic and renal responsiveness is probably mediated by receptor immaturity and/or interference of high levels of counteracting hormones present during the neonatal period.

Animals↗

PubMed1992

Renal effects of dopamine and dopexamine in the newborn anesthetized rabbit.

The renal effects of dopexamine, a new dopaminergic agonist with marked beta 2-adrenergic agonist properties, but no alpha-adrenergic effect, has been studied in 8 newborn New Zealand rabbits, whose renal functional characteristics show close similarities with those of premature infants. Six animals were used as controls. After a control period, dopexamine was infused intravenously at a rate of 4 micrograms/kg per min and after a wash-out period, at 10 micrograms/kg per min. The renal effects of dopamine were studied in similar conditions. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined by inulin and para-aminohippuric acid clearances, respectively. Dopexamine, 4 micrograms/kg per min, did not induce changes in cardiovascular and renal hemodynamics or in renal functions. At 10 micrograms/kg per min, a significant increase in urine flow rate (25 +/- 5%; p less than 0.01), urine sodium excretion (77 +/- 17%; p less than 0.01) and fractional sodium excretion (69 +/- 25%; p less than 0.05) was observed. The GFR, RPF and renal vascular resistance (RVR) were not affected. Heart rate increased slightly but significantly (8 +/- 3%; p less than 0.05), without change in mean blood pressure (MBP). Dopamine, 4 micrograms/kg per min, decreased slightly albeit significantly MBP (3 +/- 1%; p less than 0.05). At 10 micrograms/kg per min the only renal effect was a significant increase in RVR (19 +/- 6%; p less than 0.02). The different actions of these two dopaminergic agonists in this immature model could be explained by their respective ability to activate electively the adrenergic and dopaminergic peripheral receptors. The natriuretic and diuretic effect of dopexamine in normal immature rabbits, in the absence of changes in RPF or GFR is probably mediated by a direct action of this agent on dopaminergic tubular receptors. Failure of these two drugs to increase RPF may be related to an immaturity of the dopaminergic vascular receptors.

Adrenergic Agonists↗

PubMed1991

Hyperoxemia does not affect renal hemodynamics and function in newborn rabbits.

Renal hemodynamics and function were assessed in 10 anesthetized newborn rabbits undergoing acute hyperoxemia for 1 h. The hyperoxemic period either followed (group 1: n = 5) or preceded (group 2: n = 5) a normoxemic control period. Renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed by the clearance of p-aminohippuric acid and inulin, respectively. Urine flow rate, GFR, RBF, renal vascular resistance, filtration fraction and sodium fractional excretion remained unchanged throughout the study whatever the order of the normoxemic and hyperoxemic periods. It is concluded that hyperoxemia up to PaO2 of 170 mm Hg does not alter renal function.

Animals↗

PubMed1991

Failure of dopexamine to protect the hypoxemic newborn rabbit kidney.

The renal effects of dopexamine, a new dopaminergic agonist devoid of any alpha-adrenergic effect, were studied in 11 anesthetized newborn rabbits undergoing an acute hypoxemic normocapnic stress. Acute hypoxemia (PaO2 = 41 mm Hg) was associated with a marked increase in renal vascular resistance and a consequent decrease in glomerular filtration rate and renal blood flow. These changes were not modified by the administration of dopexamine at 10 micrograms/kg/min. Failure of dopexamine to blunt the hypoxemia-induced vaso-constriction suggests vascular dopaminergic receptor immaturity.

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