Nitrendipine and the Pressure-Dependent Vasodilation of Vessels in the Hydronephrotic Kidney

Steinhausen, M; Fleming, John T.; Holz, Frank G.; Parekh, N.; Dussel, R.

doi:10.1097/00005344-198700001-00008

Cited by 8 publications

(4 citation statements)

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“…Nitrendipine causes vasodilation predominantly in the preglomerular vessels, 15 which in turn increases the hydrostatic pressure for glomerular filtration. An increase in hydrostatic filtration pressure can also be achieved by postglomerular vasoconstriction.…”

Section: Discussionmentioning

confidence: 99%

Renal effects of captopril and nitrendipine in transgenic rats with an extra renin gene.

et al. 1994

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We investigated the acute effects of captopril and nitrendipine on renal function and sodium excretion in hypertensive, male, heterozygous transgenic rats harboring a mouse renin gene [TGR(mRen-2)27]. Both drugs reduced blood pressure dose dependently in conscious transgenic rats. The oral ED20 for captopril was 0.5 mg/kg and 2.7 mg/kg for nitrendipine. In orally salt-loaded (20 mL/kg saline) transgenic rats captopril (0.3 to 3.0 mg/kg) reduced sodium excretion by approximately 90% in the 6 hours after administration, whereas equally antihypertensive dsses of nitrendipine increased sodium excretion by approximately 100%. The antinatriuretic effect of captopril was accompanied by a reduction in creatinine clearance and a decrease in the excretion of cyclic GMP. In orally water-loaded (20 mL/kg water) transgenic rats captopril also reduced sodium excretion by more than 90%, N umerous genetic rat models of hypertension show abnormalities of the renin-angiotensin system. 1 However, primary and secondary changes cannot be easily distinguished in these models, which makes it difficult to establish cause and effect. Transgenic (TG) rats carry an additional mouse renin gene [TGR(mRen-2)27]. They provide a new model of hypertension with a well-defined genetic background. 2TG rats are characterized by high transcription rates of the transgene in the adrenal glands, high plasma aldosterone concentrations, suppression of renal renin production, and low plasma renin activity.2 -3 The finding of exaggerated natriuresis both in hypertensive patients with low plasma renin activity but high aldosterone concentrations 4 and in TG rats 5 suggests a clinical relevance for this new hypertension model. We therefore investigated the renal effects of antihypertensive drugs with both renin-angiotensin system-dependent and renin-angiotensin system-independent mechanisms of action in TG rats. In particular, we compared the antihypertensive and renal sodium handling effects of the angiotensin-converting enzyme inhibitor captopril and the calcium antagonist nitrendipine in TG rats. Nitrendipine was chosen because its vasodilator action is independent of the renin-angiotensin system. Both angiotensin-converting enzyme inhibitors and calcium Correspondence to Dr Claudia Hirth-Dietrich, Bayer AG, Institut fur Herzkreislauf-und Arterioskleroseforschung, D-42096 Wuppertal, Germany. and nitrendipine slightly increased sodium excretion. In control Sprague-Dawley rats the effects were opposite; namely, captopril tended to increase natriuresis, and nitrendipine caused a small but distinct decrease in sodium excretion. Intravenous captopril in anesthetized transgenic rats caused an antinatriuresis with a decrease in inulin clearance but not in Sprague-Dawley rats. To control for non-renin-related effects of captopril, we gave transgenic rats oral losartan. Losartan also decreased urinary sodium excretion. The results suggest a role for the renin-angiotensin system in the maintenance of glomerular filtration rate and sodium excretion in trans...

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Section: Discussionmentioning

confidence: 99%

Renal effects of captopril and nitrendipine in transgenic rats with an extra renin gene.

et al. 1994

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“…It has also been recently suggested that the afferent arteriole seems to be more sensitive to some calcium antagonists than the efferent arteriole [9]. More exactly, NIF a di hydropyridine-derived calcium channel blocker, produces a preglomerular vasodilatation [10].…”

Section: Discussionmentioning

confidence: 99%

“…In our attempt to reduce this nephrotoxicity, we evalu ate the protective effect of nifedipine (NIF) in the rat, as this drug, like other dihydropyridine calcium channel blockers, is known to have vasoactive effects on the kidney [9,10).…”

Section: Introductionmentioning

confidence: 99%

Nifedipine and Amphotericin B Nephrotoxicity in the Rat

Soupart¹,

Decaux²

1989

Nephron

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Amphotericin B nephrotoxicity limits its therapeutic use. The mechanisms involved in the deleterious effect on the kidney include a preglomerular vasoconstriction. Nifedipine, a calcium antagonist which acts also on the afferent arteriolar tone, did not, however, prevent renal impairment in the rats of our study. This could be due either to a negligible role of the hemodynamic changes in the development of renal failure or to a lack of efficacy of nifedipine on the vasoconstrictor mechanism induced by amphotericin B.

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“…Experimental hydronephrosis in rats can be induced by the ligation of the ureter (Gobe & Axelsen, 1987). Previous studies have shown that hydronephrosis, congenital, or surgically induced, can promote the development of other diseases (Carlström et al., 2006; Seely et al., 2018), can alter the functioning of other organs (Arnold et al., 2011; Marsh et al., 2007) and may be responsible for different responses to a given treatment (Steinhausen et al., 1987).…”

Section: Introductionmentioning

confidence: 99%

Rats with congenital hydronephrosis show increased susceptibility to renal ischemia‐reperfusion injury

et al. 2020

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Many drug candidates have shown significant renoprotective effects in preclinical models; however, there is no clinically used effective pharmacotherapy for acute kidney injury. The failure to translate from bench to bedside could be due to misleading results from experimental animals with undetected congenital kidney defects. This study was performed to assess the effects of congenital hydronephrosis on the functional capacity of tubular renal transporters as well as kidney sensitivity to ischemia‐reperfusion (I‐R)‐induced injury in male Wistar rats. Ultrasonography was used to distinguish healthy control rats from rats with hydronephrosis. L‐carnitine or furosemide was administered, and serial blood samples were collected and analyzed to assess the effects of hydronephrosis on the pharmacokinetic parameters. Renal injury was induced by clamping the renal pedicles of both kidneys for 30 min with subsequent 24 hr reperfusion. The prevalence of hydronephrosis reached ~30%. The plasma concentrations after administration of L‐carnitine or furosemide were similar in both groups. I‐R induced more pronounced renal injury in the hydronephrotic rats than the control rats, which was evident by a significantly higher kidney injury molecule‐1 concentration and lower creatinine concentration in the urine of the hydronephrotic rats than the control rats. After I‐R, the gene expression levels of renal injury markers were significantly higher in the hydronephrotic kidneys than in the kidneys of control group animals. In conclusion, our results demonstrate that hydronephrotic kidneys are more susceptible to I‐R‐induced damage than healthy kidneys. Unilateral hydronephrosis does not affect the pharmacokinetics of substances secreted or absorbed in the renal tubules.

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Nitrendipine and the Pressure-Dependent Vasodilation of Vessels in the Hydronephrotic Kidney

Cited by 8 publications

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Renal effects of captopril and nitrendipine in transgenic rats with an extra renin gene.

Renal effects of captopril and nitrendipine in transgenic rats with an extra renin gene.

Nifedipine and Amphotericin B Nephrotoxicity in the Rat

Rats with congenital hydronephrosis show increased susceptibility to renal ischemia‐reperfusion injury

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