Laboratory Investigation

Kidney International (1981) 20, 628–635; doi:10.1038/ki.1981.186

Glomerular immune injury in the rat: Effect of antagonists of histamine activity

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

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, Veterans Administration Medical Center (111H), 3350 La Jolla Village Drive, San Diego, California 92161, USA

Received 9 September 1980; Revised 23 January 1981.

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Abstract

Glomerular immune injury in the rat: Effect of antagonists of histamine activity. The participation of histamine via H1 and H2 receptors, in the alteration of glomerular ultrafiltration consequent to acute glomerular immune injury was evaluated in three groups of Munich-Wistar rats, before and after the administration of large doses of antiglomerular basement membrane antibody (AGBM). Group 1 was the control and was untreated; group 2, rats continuously infused with the H, receptor antagonist diphenhydramine; and group 3, rats receiving continuous infusion of the H2 receptor antagonist cimetidine. In group 1, nephron filtration rate (SNGFR) decreased within 60 min after AGBM from 58 plusminus 2 to 32 plusminus 5 nl dot min-1 dot g kidney wt-1 (P < 0.0005) due to decreases in both nephron plasma flow (RPF) (291 plusminus 35 to 119 plusminus 23 dot min-1 dot g kidney wt-1) (P < 0.0005) and the glomerular permeability coefficient (LPA) (0.13 plusminus 0.02 to 0.06 plusminus 0.01 nl dot sec-1 dot g kidney wt-1 dot mm Hg-1) (P < 0.01). In group 2, SNGFR decreased similarly with AGBM (59 plusminus 2 to 23 plusminus 10 nl dot min-1 dot g kidney wt-1 (P < 0.0005) due again to major reductions in RPF and LPA, suggesting no protective effect of Hi receptor blockade. In group 3, control, pre-AGBM values for SNGFR and RPF were lower than they were in groups 1 and 2 due to cimetidine infusion, SNGFR and RPF decreased but to a lesser extent in group 3 (48 plusminus 3 to 41 plusminus 4 nl dot min-1 dot g kidney wt-1) (P < 0.0005). Renal vascular resistance did not change after AGBM in this group but interpretation of this finding is complicated because blood pressure decreased after the antibody administration. LPA decreased in group 3 as in group 1, therefore neither H1 nor H2 receptor antagonist prevented reductions in LPA. The absence of vasoconstriction after AGBM during H2 receptor blockade may have been a nonspecific effect of cimetidine. Histamine plays no major role in AGBM-indueed immune injury in the rat and does not prevent a reduction in nephron filtration rate.

Lésion glomérulaire immune chez le rat: Effet des antagonistes de l'activité de l'histamine. La participation de l'histamine, via les récepteurs H1 et H2, dans les modifications de â ultrafiltration glomérulaire consécutive à une lésion glomérulaire immune aiguë a été évaluée dans trois groupes de rats Munich-Wistar, avant et après l'administration de doses élevées d'anticorps anti-membrane basale glomérulaire (AGBM); groupe 1, contrôle et non traité; groupe 2, rats soumis à une perfusion continue de diphenhydramine, antagoniste du récepteur H,; groupe 3, rats soumis à une perfusion continue de cimétidine, antagoniste du récepteur H2. Dans le groupe 1 le débit de filtration glomérulaire des néphrons individuels (SNGFR) diminue au cours des 60 min consécutives à l'administration d'AGBM de 58 plusminus 2 à 32 plusminus 5 nl dot min-1 dot g de poids de rein-1 (P < 0,0005) du fait des diminutions du débit plasmatique (RPF) (291 plusminus 35 à 119 plusminus 23 nl dot min -1 dot g poids de rein ' (P < 0,0005) et du coefficient de perméabilité glomérulaire (LPA) (0,13 plusminus 0,02 à 0,06 plusminus 0,01 nl dot sec -1 dot g poids de rein dot mm Hg-1) (P < 0,01). Dans le groupe 2, SNGFR diminue de la même façon après AGBM (59 plusminus 2 à 23 plusminus 10 nl dot min-1 dot g poids de rein-1) (P < 0,0005) du fait de diminutions importantes de RPF et LPA, ce qui suggère l'absence d'effet protecteur du blocage des récepteurs H1 Dans le groupe 3, les valeurs contrôles, pré AGBM, de SNGFR et RPF sont plus faibles que celles des groupes 1 et 2 du fait de la perfusion de cimétidine. SNGFR et RPF sont diminués dans le groupe 3 mais à un niveau moindre (48 plusminus 3 à 41 plusminus 4 nl dot min-1 dot g poids de rein-1) (P < 0,0005). La résistance vasculaire rénale ne change pas après AGBM dans ce groupe, mais l'interprétation de ce résultat est rendue difficile par la baisse de la pression artérielle après l'administration d'anticorps. LPA diminue dans le groupe 3 comme dans le groupe 1. L'absence de vasoconstriction après AGBM au cours du blocage de H2 peut avoir été un effet non spécifique de la cimétidine. L'histamine ne joue pas de rôle majeur dans la lésion immune induite par AGBM chez le rat.

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