Laboratory Investigation

Kidney International (1985) 28, 135–139; doi:10.1038/ki.1985.132

Nephrotoxic serum nephritis with hypertension: Amelioration by antihypertensive therapy

Joel Neugarten1, Bernard Kaminetsky1, Helen Feiner1, Robert G Schacht1, David T Liu1 and David S Baldwin1

1Hypertension and Renal Disease Section, New York University School of Medicine and Veterans Administration Medical Center, New York, New York, USA

Correspondence: Dr D S Baldwin, Hypertension and Renal Disease Section, New York University School of Medicine, New York, New York 10016 USA

Received 21 August 1984; Revised 6 December 1984.

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Abstract

Nephrotoxic serum nephritis with hypertension: Amelioration by antihypertensive therapy. We have examined the effects of antihypertensive therapy on glomerular dynamics and on the clinical and morphologic features of a model of nephrotoxic serum nephritis (NSN) in which hypertension occurs. NSN was induced in uninephrectomized male Sprague Dawley rats, which drak 0.9% sodium chloride ad libitum One-half were assigned randomly to a treated group whose blood pressure was normalized on a regimen of reserpine, hydralazine, and hydrochlorothiazide. Hypertension continued throughout the 6 weeks of study in untreated rats (blood pressure 148 plusminus 5 vs. 103 plusminus 3 mm Hg in treated rats, P < 0.01). Urinary protein excretion was greater (437 plusminus 110 vs. 254 plusminus 81 mg/24 hr, P < 0.005), and serum albumin lower (1.6 plusminus 0.4 vs. 2.9 plusminus 0.3 g/dl, P < 0.01) in hypertensive animals. Diffuse glomerular endo- and extracapillary proliferation and arteriolar medial hypertrophy were observed frequently in nephritic rats with untreated hypertension. By contrast, structural abnormalities were limited primarily to focstl segmental proliferation involving fewer than one-third of glomeruli in the absence of vascular changes in treated normotensive rats. Micropuncture studies performed 8 to 16 days after induction of nephritis showed a reduction in glomerular capillary pressure (46 plusminus 1 vs. 55 plusminus 1 mm Hg, P < 0.001), glomerular plasma flow rate (115 plusminus 20 vs. 160 plusminus 20 nl/min, P < 0.01), and single nephron filtration rate (42 plusminus 4 vs. 56 plusminus 5 nl/min, P < 0.001) with antihypertensive treatment, suggesting that a hemodynamic mechanism may have been responsible for enhanced glomerular injury in the hypertensive nephritic animals.

Néphrite sérique néphrotoxique avec hypertension: Amélioration par le traitement antihypertenseur. Nous avons examiné les effets d'un traitement antihypertenseur sur la dynamique glomérulaire et les caractéristiques cliniques et morphologiques d'un modèle de néphrite sérique néphrotoxique (NSN) au cours duquel une hypertension survient. La NSN a été induite chez des rats mâles Sprague-Dawley uninéphrecto-misés, qui buvaient du chlorure de sodium à 0,9% ad libitum. La moitié ont été assignés au hasard à un groupe de traitement dont la pression sanguine était normalisée par une association de réserpine, d'hydralazine, et d'hydrochlorothiazide. L'hypertension a persisté pendant les 6 semaines de l'étude chez des rats non traités (pression sanguine 148 plusminus 5 contre 103 plusminus 3 mm Hg chez les rats traités, P < 0,001). La protéinurie était plus forte (437 plusminus 110 contre 254 plusminus 81 mg/24 hr, P < 0,005), et l'albuminémie plus basse (1,6 plusminus 0,4 contre 2,9 plusminus 0,3 g/dl, P < 0,01) chez les animaux hypertendus. Une prolifération glomérulaire diffuse endo- et extra-capillaire et une hypertrophie médiale artériolaire étaient communément observés chez les rats néphritiques avec hypertension non traités. A l'opposé, les anomalies structurelles étaient généralement limitées à une prolifération segmentaire et focale portant sur moins d'un tiers des glomérules en l'absence de changements vasculaires chez les rats normotendus traités. Des études de microponction faites 8 à 16 jours après induction de la néphrite ont montré une réduction de la pression capillaire glomérulaire (46 plusminus 1 contre 55 plusminus 1 mm Hg, P < 0,001), du flux plasmatique glomérulaire (115 plusminus 20 contre 160 plusminus 20 nm/min, P < 0,01) et du débit de filtration glomérulaire individuel (42 plusminus 4 contre 56 plusminus 5 nl/min, P < 0,001) avec le traitement antihypertenseur, suggérant un mécanisme hémodynamique qui pourrait avoir été responsable de la stimulation des lésions glomérulaires chez les animaux néphritiques hypertendus.

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