AUTOLOGOUS IMMUNE COMPLEX NEPHRITIS AND DOCA‐NaCl LOAD: A NEW MODEL OF HYPERTENSION

Abstract

In order to explore immunological features of hypertension, we studied autologous immune complex nephritis (Heymann nephritis) combined with DOCA‐NaCl treatment. This combination resulted in hypertension and increased heart weight whereas DOCA‐NaCl treatment alone induced only a slight elevation of blood pressure and a moderate increase in heart weight. Nephritic rats without DOCA‐NaCl load remained normotensive, their heart weights being comparable to those of controls. This new model of hypertension was neither characterized by azotemia nor by reduced renal excretory capacity. Hypertension was not renin‐angiotensin‐dependent. DOCA‐NaCl treatment accelerated the development of proteinuria. In the hypertensive rats, systolic blood pressure correlated to daily urinary protein excretion. Renal histopathology revealed changes resembling those of malignant nephrosclerosis. Immunohistology and electron microscopy showed a typical membranous glomerulonephritis in all immunized animals. It was concluded that immune complex disease of the Heymann nephritis type may interfere with normal hemodynamic adaptation to hypervolemic sodium load, resulting in hypertension.

IMMUNOLOGICAL AND ENDOCRINE FEATURES OF A NEW EXPERIMENTAL HYPERTENSION MODEL: HEYMANN NEPHRITIS‐DOCA‐NaCl HYPERTENSION

“…e have t h e r e f o r e s t u d i e d whether autoimmune n e p h r i t i s o f t h e Heymann n e p h r i t i s t y p e would i n f l u e n c e t h e course o f experimental hypertension i n t h e r a t . We d e s c r i b e immunologi c a l and endocrine features o f t h e Heymann nephritis-DOCA-NaC1 hypertension, introduced as a new model o f hypertension (11). I n a d d i t i o n , t h e hypertensi v e e f f e c t o f Heymann n e p h r i t i s i n DOCA-NaC1 t r e a t e d r a t s i s compared w i t h i t s e f f e c t i n spontaneously hypertensive r a t s (SHR).…”

“…To induce Heymann n e p h r i t i s , r a t s 2 112-3 months o l d were immunized w i t h i s o l a t e d r a t kidney brush border (BB) f r a c t i o n as described (11). N,N'-DAB nephropathy, used as a model o f non-immunological r e n a l disease (17), was induced by weekly i n t r a p e r i t o n e a l i n j e c t i o n s o f 10-20 rng o f N,N'-DAB (10).…”

“…Blood pressure was recorded i n conscious animals by a t a i l c u f f method as described (11). Plasma r e n i n a c t i v i t y (PRA) was determined by r a d i oimmunoassay modified f o r r a t plasma (12).…”

“…Plasma r e n i n a c t i v i t y (PRA) was determined by r a d i oimmunoassay modified f o r r a t plasma (12). Hematocrit, and serum and u r i n e concentrations o f sodium, potassium, c r e a t i n i n e , and t o t a l p r o t e i n were measured as described (11). Serum anti-BB a n t i b o d i e s were determined by i n d i r e c t immunofluorescence technique ( 8 ) .…”

“…Serum anti-BB a n t i b o d i e s were determined by i n d i r e c t immunofluorescence technique ( 8 ) . Kidneys were s t u d i e d h i s t o l og i c a l l y , immunohistological l y and by e l e c t r o n microscope as r e p o r t e d (8,11). Student's t -t e s t f o r p a i r e d o r non-paired observations was a p p l i e d…”