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

Glomerular immune injury in the rat: The influence of angiotensin II and α-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 (L p A). We have examined the participation of angiotensin II (AII) and α-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 sar 1 -ala 8 -AII (1 µg · kg of body wt -1 · min -1 ), an AII receptor antagonist; and group 3, rats receiving continuous infusion of phentolamine (27 µg · kg body wt -1 · min -1 ), a dose sufficient to block α-adrenergic responses. In group 1, SNGFR decreased from 58 ± 4 to 35 ± 6nl · min -1 · g kidney wt -1 (P > 0.001) after anti-GBM administration due to reductions in RPF (272 ± 35 to 170 ± 52nl · min -1 · g of kidney wt -1 , P > 0.0001) and L p A (0.13 ± 0.03 to 0.04 ± 0.01nl · sec -1 · g of kidney wt -1 · mm Hg -1 , P > 0.02). In group 2, the sar 1 -ala 8 -AII-infused rats, SNGFR decreased to a greater extent than it did in group 1 (P > 0.01) (55 ± 2 to 18 ± 6nl · min -1 · g of kidney wt -1 , P > 0.005) due to a greater reduction in RPF and a similar decrease in L p A. In group 3, phentolamine infusion prevented the decrease in SNGFR (52 ± 3 to 52 ± 4nl · min -1 · g of kidney wt -1 , NS) due primarily to elimination of vasoconstriction and a significantly lesser reduction in L p A (0.10 ± 0.02 to 0.07 ± 0.01nl · sec -1 · g of kidney wt -1 · 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 L p A. α-Adrenergic blockade (1) prevents acute immune induced vasoconstriction and (2) partially prevents the immune induced reduction in L p A. Lesion glomerulaire immunologique chez le rat. Influence des inhibiteurs de l'angiotensine II et α-adrenergique. Le debit de filtration glomerulaire individuel (SNGFR) diminue significativement apres l'administration de fortes doses d'anticorps antimembrane basale (anti-GBM) glomerulaire en raison de la diminution du debit plasmatique (RPF) et du coefficient de permeabilite glomerulaire (L p A). Nous avons etudie la participation de l'angiotensine II (AII) et de l'activite α-adrenergique dans ce processus chez trois groupes de rats Munich-Wistar: groupe 1, controles et non traites; groupe 2, des rats recevant une perfusion continue de sar 1 -ala 8 -AII (1 µg · kg of body wt -1 · min -1 ), un antagoniste des recepteurs de l'AII; et groupe 3, des rats recevant une perfusion continue de phentolamine (27 µg · kg of body wt -1 · min -1 ), une dose suffisante pour bloquer les reponses α-adrenergiques. Dans le groupe 1, SNGFR diminue de 58 ± 4 a 35 ± 6nl · min -1 · g of kidney wt -1 , (P -1 · g of kidney wt -1 , P p A (0,13 ± 0,03 a 0,04 ± 0,01nl · sec -1 · g of kidney wt -1 · mmHg -1 , P 1 -ala 8 -AII, SNGFR a diminue plus que dans le groupe 1 (P -1 · g of kidney wt -1 , P p A. Dans le groupe 3, la perfusion de phentolamine a empeche la diminution de SNGFR (52 ± 3 a 52 ± 4nl · min -1 · g of kidney wt -1 , NS) du fait de l'elimination de la vasoconstriction et d'une diminution significativement moindre de L p A (0,10 ± 0,02 a 0,07 ± 0,01nl · sec -1 · g of kidney wt -1 · mm Hg -1 ). Il n'a pas ete observe de differences morphologiques particulieres en groupe 3 apres anticorps anti-GBM. Le blocage de l'activite de Ail n'empeche pas la vasoconstriction a determinisme immun ou la reduction de L p A. Le blocage α-adrenergique (1) empeche la vasodilatation aigue a determinisme immun et (2) empeche partiellement la reduction de L p A a determinisme immun.