Laboratory Investigation

Kidney International (1981) 20, 452–461; doi:10.1038/ki.1981.161

Glomerular immune injury in the rat: The influence of angiotensin II and alpha-adrenergic inhibitors

Roland C Blantz, Bryan J Tucker, Leslie C Gushwa, Örjan W Peterson and Curtis B Wilson

Department of Medicine, University of California, San Diego School of Medicine, and Veterans Administration Medical Center, San Diego, and Department of Immunopathology, Scripps Clinic and Research Foundation, La Jolla, California

Correspondence: Dr R C Blantz, Department of Medicine, Veterans Administration Medical Center (111H), 3350 La Jolla Village Drive, San Diego, California 92161, USA

Received 9 September 1980; Revised 19 January 1981.

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Abstract

Glomerular immune injury in the rat: The influence of angiotensin II and alpha-adrenergic inhibitors. Nephron filtration rate (SNGFR) decreases significantly after the administration of large doses of antigiomerular basement membrane antibody (anti-GBM) as a result of reductions in both nephron (renal) plasma flow (RPF) and the glomerular permeability coefficient (LpA). We have examined the participation of angiotensin II (AII) and alpha-adrenergic activity in this process in paired studies in three groups of Munich-Wistar rats: group 1, control and untreated; group 2, rats receiving continuous infusion of sar1-ala8-AII (1 microg dot kg of body wt-1 dot min-1), an AII receptor antagonist; and group 3, rats receiving continuous infusion of phentolamine (27 microg dot kg body wt-1 dot min-1), a dose sufficient to block alpha-adrenergic responses. In group 1, SNGFR decreased from 58 plusminus 4 to 35 plusminus 6 nl dot min-1 dot g kidney wt-1 (P > 0.001) after anti-GBM administration due to reductions in RPF (272 plusminus 35 to 170 plusminus 52 nl dot min-1 dot g of kidney wt-1, P > 0.0001) and LpA (0.13 plusminus 0.03 to 0.04 plusminus 0.01 nl dot sec-1 dot g of kidney wt-1 dot mm Hg-1, P > 0.02). In group 2, the sar1-ala8-AII-infused rats, SNGFR decreased to a greater extent than it did in group 1 (P > 0.01) (55 plusminus 2 to 18 plusminus 6 nl dot min-1 dot g of kidney wt-1, P > 0.005) due to a greater reduction in RPF and a similar decrease in LpA. In group 3, phentolamine infusion prevented the decrease in SNGFR (52 plusminus 3 to 52 plusminus 4 nl dot min-1 dot g of kidney wt-1, NS) due primarily to elimination of vasoconstriction and a significantly lesser reduction in LpA (0.10 plusminus 0.02 to 0.07 plusminus 0.01 nl dot sec-1 dot g of kidney wt-1 dot mm Hg-1). There were no morphologic differences after anti-GBM administration that were unique to group 3. Blockade of AII activity does not prevent immune induced vasoconstriction or the reduction in LpA. alpha-Adrenergic blockade (1) prevents acute immune induced vasoconstriction and (2) partially prevents the immune induced reduction in LpA.

Lésion glomérulaire immunologique chez le rat. Influence des inhibiteurs de l'angiotensine II et alpha-adrénergique. Le débit de filtration glomérulaire individuel (SNGFR) diminue significativement après l'administration de fortes doses d'anticorps antimembrane basale (anti-GBM) glomérulaire en raison de la diminution du débit plasmatique (RPF) et du coefficient de perméabilité glomérulaire (LpA). Nous avons étudié la participation de l'angiotensine II (AII) et de l'activité alpha-adrénergique dans ce processus chez trois groupes de rats Munich-Wistar: groupe 1, contrôles et non traités; groupe 2, des rats recevant une perfusion continue de sar1-ala8-AII (1 microg dot kg of body wt-1 dot min-1), un antagoniste des récepteurs de l'AII; et groupe 3, des rats recevant une perfusion continue de phentolamine (27 microg dot kg of body wt-1 dot min-1), une dose suffisante pour bloquer les réponses alpha-adrénergiques. Dans le groupe 1, SNGFR diminue de 58 plusminus 4 à 35 plusminus 6 nl dot min-1 dot g of kidney wt-1, (P < 0,001) après anticorps anti-GBM du fait de la diminution de RPF (272 plusminus 35 à 170 plusminus 52 nl dot min-1 dot g of kidney wt-1, P < 0,0001) et LpA (0,13 plusminus 0,03 à 0,04 plusminus 0,01 nl dot sec-1 dot g of kidney wt-1 dot mmHg-1, P < 0,02). Dans le groupe 2, chez les rats perfuses avec sar1-ala8-AII, SNGFR a diminué plus que dans le groupe 1 (P < 0,01) (55 plusminus 2 à 18 plusminus 6 nl dot min-1 dot g of kidney wt-1, P < 0,005) du fait d'une plus grande diminution de RPF et d'une diminution semblable de LpA. Dans le groupe 3, la perfusion de phentolamine a empêché la diminution de SNGFR (52 plusminus 3 à 52 plusminus 4 nl dot min-1 dot g of kidney wt-1, NS) du fait de l'élimination de la vasoconstriction et d'une diminution significativement moindre de LpA (0,10 plusminus 0,02 à 0,07 plusminus 0,01 nl dot sec-1 dot g of kidney wt-1 dot mm Hg-1). Il n'a pas été observé de differences morphologiques particulières en groupe 3 après anticorps anti-GBM. Le blocage de l'activité de Ail n'empêche pas la vasoconstriction à déterminisme immun ou la réduction de LpA. Le blocage alpha-adrénergique (1) empêche la vasodilatation aiguë à déterminisme immun et (2) empëche partiellement la réduction de LpA à déterminisme immun.

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