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 H1 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 +/- 2 to 32 +/- 5 nl . min-1 . g kidney wt-1 (P less than 0.0005) due to decreases in both nephron plasma flow (RPF) (291 +/- 35 to 119 +/- 23 nl . min-1 . g kidney wt-1) (P less than 0.0005) and the glomerular permeability coefficient (LpA) (0.13 +/- 0.02 to 0.06 +/- 0.01 nl . sec-1 . g kidney wt-1 . mm Hg-1) (P less than 0.01). In group 2, SNGFR decreased similarly with AGBM (59 +/- 2 to 23 +/- 10 nl . mm-1 . g kidney wt-1) (P less than 0.0005) due again to major reductions in RPF and LpA, suggesting no protective effect of H1 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 +/- 3 to 41 nl . min-1 . g kidney wt-1) (P less than 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-induced immune injury in the rat and does not prevent a reduction in nephron filtration rate.
D000818:Animals; D000906:Antibodies; D001485:Basement Membrane / Q000276:immunology; D001794:Blood Pressure; D002463:Cell Membrane Permeability; D002927:Cimetidine / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000209:etiology*; D006632:Histamine / Q000502:physiology*; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011968:Receptors, Histamine / Q000187:drug effects; D012079:Renal Circulation; D014655:Vascular Resistance
D000906:Antibodies; D011968:Receptors, Histamine; D002927:Cimetidine; D006632:Histamine; D004155:Diphenhydramine