Effects of Perindopril and Hydrochlorothiazide on the Long‐Term Progression of Lithium‐Induced Chronic Renal Failure in Rats

Christensen, Sten; Shalmi, Michael; Hansen, Axel Kornerup; Marcussen, Niels

doi:10.1111/j.1600-0773.1997.tb00386.x

Cited by 11 publications

(10 citation statements)

References 29 publications

(37 reference statements)

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“…Systolic arterial pressure (SAP) was measured in conscious rats using the pneumatic tail-cuff method (WϩW Blood pressure reporter, model 8006, Ugo Basile) (10). SAP was measured in the same four groups of rats as in the series of RBF measurements (SD-C, SD-T, SHR-C, and SHR-T).…”

Section: Measurement Of Arterial Pressure In Conscious Ratsmentioning

confidence: 99%

NO-independent mechanism mediates tempol-induced renal vasodilation in SHR

Richelieu¹,

Sørensen²,

Holstein‐Rathlou³

et al. 2005

American Journal of Physiology-Renal Physiology

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. NO-independent mechanism mediates tempol-induced renal vasodilation in SHR. Am J Physiol Renal Physiol 289: F1227-F1234, 2005. First published July 20, 2005; doi:10.1152/ajprenal.00116.2005.-We investigated whether tempol, a superoxide dismutase mimetic, affected renal hemodynamics and arterial pressure in spontaneously hypertensive rats (SHR) and Sprague-Dawley (SD) rats. We also examined whether tempol affected exaggerated renal vasoconstrictor responses to ANG II in SHR. To test whether the effects of tempol were due to a restored NO system, we used the NOS inhibitor N w -nitro-L-arginine methyl ester (L-NAME). Renal blood flow (RBF) and mean arterial pressure (MAP) were measured in vivo by electromagnetic flowmetry and arterial catheterization in 10-to 12-wk-old anesthetized SHR and SD rats. Systolic arterial pressure (SAP) was measured in conscious rats using the tail cuff method. Tempol (1 mM) was given in the drinking water to SD (SD-T) and SHR (SHR-T) for 5-7 days for RBF measurements and for 15 days for SAP measurements. Age-matched SD (SD-C) and SHR (SHR-C) were used as controls. ANG II (1-4 ng) was administered as a bolus via a renal artery catheter. L-NAME was administered intravenously for 15-20 min. Renal vascular resistance (RVR) was elevated in SHR-C compared with SD-C. In SHR-T, baseline RVR was not different from SD-C and SD-T rats. Tempol had no effect on RVR in SD. L-NAME elevated RVR to the same extent in all four groups. Arterial pressure was not affected by tempol. The RVR responses to ANG II were higher in SHR-C than in the SD-C group. ANG II responses were not different between SHR-T and SD-T. Overall, tempol reduced the renovascular responses to ANG II in SHR. L-NAME elevated the effects of ANG II in SD-C rats but had no effect on the ANG II responses in the other groups. Thus L-NAME treatment did not influence tempol's effects on baseline RVR or ANG II responses. We conclude that in SHR, tempol has a significant renal vasodilator effect and that it normalizes the increased renovascular ANG II sensitivity. As the effects of L-NAME are not greater in SHR-T rats, it is not likely that the elevated renal resistance and ANG II sensitivity in SHR are due to reactive oxygen speciesinduced quenching of nitric oxide. angiotensin II; hypertension; nitric oxide; oxidative stress; renal hemodynamics; spontaneously hypertensive rats KIDNEY FUNCTION IS of central importance in the control of normal blood pressure and in the development of essential hypertension (35,36). Spontaneously hypertensive rats (SHR) have an elevated renal vascular tone compared with normotensive rats (7,14,24). Also, an augmented response to vasoconstrictors, among them ANG II, has been observed in the genetically hypertensive rats (8,14,15,26,50). Despite intensive research, the reason for this enhanced renal vascular tone and reactivity in hypertensive animals is still not resolved.Elevated oxidative stress and high levels of reactive oxygen species (ROS) have been suggested to play a role in the pathogenesis of hyperten...

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Section: Measurement Of Arterial Pressure In Conscious Ratsmentioning

confidence: 99%

NO-independent mechanism mediates tempol-induced renal vasodilation in SHR

Richelieu¹,

Sørensen²,

Holstein‐Rathlou³

et al. 2005

American Journal of Physiology-Renal Physiology

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“…The material used in the present study originates from a functional and morphometric study which was published previously (9), but none of the data has been published before.…”

Section: Methodsmentioning

confidence: 99%

“…Inulin clearance was measured in unanesthetized rats using the constant infusion technique with 3Hlabeled inulin (9).…”

Section: Inulin Clearancementioning

confidence: 99%

“…In our early studies of lithium nephropathy in the newborn rat model we did not observe glomerulosclerosis, possibly due t o the relatively short duration (16 weeks) of the experiment. In a recent study the newborn rats were treated with lithium for 16 weeks and observed for another 24 weeks, and excessive albuminuria developed in the rats with the most severe reduction in renal function (9). This suggested that glomerular changes may develop along with the severe tubulointerstitial changes and the presence of atubular glomeruli.…”

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confidence: 99%

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Glomerular structure in lithium‐induced chronic renal failure in rats

Guo

Christensen

Marcussen

et al. 2000

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The effects of long-term lithium administration on glomerular structure and intervention with angiotensin converting enzyme inhibitor (ACEI) were studied in rats. Male Wistar rats were fed a lithium-containing diet (Li) or control diet (C) for 16 weeks postnatally. Li-treated rats developed renal failure, hypertension and proteinuria. During the subsequent 24 weeks, subgroups were treated with ACEI. The kidneys were fixed by perfusion, and tissue blocks were serially cut for estimation of glomerular volume and glomerular characteristics by light microscopy. Mesangial and mesangial matrix volume fractions, surface density of capillary walls, basement membrane thickness and foot process width (FPW) were measured by electron microscopy. Glomerular volume was decreased in Li-rats, with increased intra-individual variation. In all Li-rats, some glomeruli (mean 27%) were abnormal, with severe changes in only three rats. Ultrastructural parameters obtained by systematic sampling of three glomeruli in each rat showed no differences among groups. Among Li-treated animals there was a significant correlation between FPW and albumin excretion per unit filtration surface, and between filtration surface per glomerulus and inulin clearance. In conclusion, long-term lithium administration to newborn rats caused marked changes in glomerular volume which were not associated with measurable changes in structural parameters. No effect of ACEI-treatment was detectable.

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“…Perindopril has been shown to have various drug-drug interactions with diuretics (18,19), gentamicin (20) and lithium (21,22). However, there have been limited studies regarding the interactions between perindopril and natural Table II.…”

Section: Discussionmentioning

confidence: 99%

Effects of Chungsinoryungsan, a polyherbal complex, on the pharmacokinetic profiles of perindopril in rats

et al. 2014

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Abstract. For sufficient antihypertension with less adverse effects, numerous clinical trials have recommended combination therapy using two or more hypertensive drugs. Chungsinoryungsan (CSORS) is a polyherbal complex based on oriental medicine, which has shown therapeutic potentials for antihypertension and additional renal improvement. Therefore, the affect of CSORS on the pharmacokinetic profiles of perindopril, an antihypertensive drug, was analyzed as a novel combination of hypertensive drugs. Rats received perindopril with CSORS as the combination or distilled water as the control. The co-administration of perindopril with CSORS or distilled water was performed by single dosing or repeated dosing for a week at a 2-h interval. The analyzed pharmacokinetic parameters included peak concentration (C max ), time to reach the C max (T max ), area under the plasma concentration-time curve, terminal half-life (t 1/2 ) and mean residence time to infinity (MRT inf ). In the single oral co-administration within 5 min, the pharmacokinetics of perindopril demonstrated an increased T max and MRT inf but reduced t 1/2 in the combination compared to the control treatment, indicating drug-drug interactions between perindopril and CSORS. However, in the repeated co-administration for a week at a 2-h interval, which was more than perindopril MRT inf in the control treatment (1.5±0.1 h), the initial co-administration showed no differences in the pharmacokinetics between the combination and control treatments.Furthermore, the repeated co-administration also showed no differences between the combination and control treatment. The results indicate that CSORS can be co-administered at a 2-h interval that was more than perindopril MRT inf and further clinical studies may provide detailed information for developing a drug regimen that generates enhanced combination effects of CSORS with hypertensive drugs.

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Effects of Perindopril and Hydrochlorothiazide on the Long‐Term Progression of Lithium‐Induced Chronic Renal Failure in Rats

Cited by 11 publications

References 29 publications

NO-independent mechanism mediates tempol-induced renal vasodilation in SHR

NO-independent mechanism mediates tempol-induced renal vasodilation in SHR

Glomerular structure in lithium‐induced chronic renal failure in rats

Effects of Chungsinoryungsan, a polyherbal complex, on the pharmacokinetic profiles of perindopril in rats

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