Glomerulonephritis in Pressor Drug-Enhanced Serum Sickness of Rabbits.

Abstract

In a recent investigation(1) it was found that repeated intravenous injections of blood pressure elevating drugs following a single large intravenous injection of horse serum in rabbits regularly caused marked enhancement of the lesions of serum sickness and the appearance of manifestations, such as verrucous endocarditis and acute synovitis, not ordinarily seen in this experimental condition. Glomerulonephritis when present was unusually severe but its incidence was not significantly increased.In the present study pressor agents were @en at 2 time intervals only, either shortly after intravenous injection of foreign serum when the concentration of circulating antigen in the blood stream is high or shortly before the development of serum sickness when antibodies appear in increasing concentration. Unexpectedly, it was found that the incidence of glomerulonephritis was greatly influenced by the time of administration of blood pressure elevating drugs. The present report records this finding.Materials and methods. Thirty-four young adult rabbits weighing from 1800 to 2500 g were injected intravenously with 15 cc/kg body weight of whole pooled horse serum (Difco) . Eleven of these were injected intravenously with 0.1 cc levophed (0.2% levartereonal bitartrate, Winthrop) a t 2 hours, 0.1 cc aramine (10 mg/ml metaraminal bitartrate, Merck Sharp and Dohme) at 4 hours and 0.1 cc adrenalin ( 1 mg/ml epinephrine hydrochloride, Parke Davis Co.) at 6 hours after horse serum injection. They were given 3 injections in the same order 2 hours apart on the second day. Eleven other rabbits were given the same sequence of 3 injections at 2-hour intervals on the sixth, seventh and eighth days after horse serum injection. The remaining 12 rabbits were given a t0ta.l of *Aided by Research Grant H-1088 from Nat. Heart Inst. of Nat. Inst. Health, U.S.P.H.S., Bethesda, Md.12 injections of pressor agents, 3 on the first day and 3 on each of the 6th, 7th and 8th days after horse serum administration. The dosage and time intervals between injections were kept constant.The days of injection of pressor agents were staggered in this way to determine a t what period they might have an effect on the development of glomerular damage. Immediately after injection of horse serum, antigen levels in the circulation are high but insignificant amounts of antibody have formed. During the 6th to 8th days, however, antigen levels drop rapidly and antibody levels rise (293) -Three different pressor agents were used because each is believed to cause elevation of blood pressure in a somewhat different manner. It is well known that rabbits rapidly become tolerant to repeated adrenalin injections and will not respond unless the dose is continuously increased. It was hoped that the use of 3 agents would elicit more consistent responses to each one. Blood pressure readings by the ear capsule method were attempted but did not yield reliable results because the central ear arteries usually contracted promptly after injection of the pressor agents.The doses employ...

Captopril Treatment of Hypertension and Renal Failure in Systemic <i>Lupus erythematosus</i>

“…Firstly, it is a well-known fact that the progres sion of renal disease is enhanced if the blood pressure is poorly controlled [2]. Secondly, animal studies indicate that renal damage in experimental immune complex nephritis is more severe if hypertension is induced in the animals at the same time [3][4][5].…”

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

“…Giese (1 4) has shown that during experimentally induced angiotensin hypertension the vascular lesions appear in the areas of dilated arterioles and that increased permeability to plasma components and possibly ischemia of the vascular wall are important in this context. The lesions of experital serum sickness are aggravated by high blood pressure (38). This may explain why immune complex nephritis together with DOCA-NaCI load exceeds the glomerular and vascular tolerance, resulting in irreversible injury.…”

Role of Glomerular Basement Membrane Thixotropy and Influence of Glomerular Vascular Pressure in the Pathogenesis of Immune Complex-Induced Glomerulonephritis

“…' Although it was not stated just how glomerulonephritis was prevented, their conclusion clearly associated glom erular pressure, transit of complexes through vascular walls, and the development of glomerulonephritis without involving inflammatory reactions, fibrin deposition, anti basement membrane antibody or any other external fac tor. The importance of vascular pressure had been shown earlier [35] when it was shown that immune complex de position was enhanced in animals treated with pressor agents, and as a result glomerulonephritis of increased severity developed. Natural models of the effects of the lowered intrarenal blood pressure which follow renal ar tery obstruction have been described.…”