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 antiglomerular 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 microgram . kg of body wt-1 . min-1), and AII receptor antagonist; and group 3, rats receiving continuous infusion of phentolamine (27 micrograms . kg body wt-1 . min-1), a dose sufficient to block alpha-adrenergic responses. In group 1, SNGFR decreased from 58 +/- 4 to 35 +/- 6 nl . min-1 . g kidney wt-1 (P less than 0.001) after anti-GMB administration due to reductions in RPF (272 +/- 35 to 170 +/- 52 nl . min-1 . g of kidney wt-1, P less than 0.0001) and LpA (0.13 +/- 0.03 to 0.04 +/- 0.01 nl . sec-1 . g of kidney wt-1 . mm Hg-1, P less than 0.02). In group 2, the sar1-ala8-AII-infused rats. SNGFR decreased to a greater extent than it did in group 1 (P less than 0.01) (55 +/- 2 to 18 +/- 6 nl . min-1 . g of kidney wt-1, P less than 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 +/- 3 to 52 +/- 4 nl . min-1 . g of kidney wt-1, NS) due primarily to elimination of vasoconstriction and a significantly lesser reduction in LpA (0.10 +/- 0.02 to 0.07 +/- 0.01 nl . 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 LpA. alpha-Adrenergic blockage (1) prevents acute immune induced vasoconstriction and (2) partially prevents the imune induced reduction in LpA.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006874:Hydrostatic Pressure; D007678:Kidney Glomerulus / Q000098:blood supply / Q000276:immunology*; D007958:Leukocyte Count; D009504:Neutrophils / Q000276:immunology; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012504:Saralasin / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000906:Antibodies; D000804:Angiotensin II; D012504:Saralasin; D010646:Phentolamine