Protective effects of valsartan and benazeprilat in salt-loaded stroke-prone spontaneously hypertensive rats.

These experiments examined the effectiveness of chronic blockade of the renin angiotensin system with either valsartan or benazeprilat on survival, blood pressure and end-organ damage in salt-loaded stroke-prone SHR. Valsartan or benazeprilat given continuously by subcutaneous osmotic minipump beginning at 10.5 weeks of age lowered blood pressure, as determined by radiotelemetry, prevented proteinuria, prolonged survival and decreased the severity of histopathological changes in the heart and kidney. These results indicate that angiotensin receptor blockade affords a similar degree of protection as inhibition of angiotensin converting enzyme in salt-loaded stroke-prone SHR. Furthermore, our results are consistent with a primary contribution of angiotensin II to the maintenance of blood pressure and support a principal role for angiotensin II-dependent mechanisms in the development of end-organ damage in the salt-loaded stroke-prone SHR.

Protective effects of CGS 30440, a combined angiotensin-converting enzyme inhibitor and neutral endopeptidase inhibitor, in a model of chronic renal failure.

The purpose of these studies was to compare the effects of CGS 30440 (CGS), a dual angiotensin-converting enzyme inhibitor (ACEI)/neutral endopeptidase inhibitor (NEPI) to benazepril (BZ), an ACEI, in a model of five-sixths nephrectomy. The doses of BZ and CGS 30440 tested were 6.5 micromol/kg/day and 2.2 micromol/kg/day. Drugs or vehicle (V) were administered subcutaneously for 6 weeks with dosing initiated 1 week after renal mass reduction. At 6 weeks of receiving drug (7 weeks after five-sixths nephrectomy), CGS/6.5 and BZ/6.5 and CGS/2.2 maintained systolic blood pressures (SBP) at presurgical values. BZ/2.2 did not reduce SBP and was similar to the V group. Urinary protein excretion increased >10-fold in the V-treated group. BZ, at either dose, reduced the proteinuria slightly. CGS/6.5 and CGS/2.2 caused significant (p < 0.05) reductions in proteinuria. Creatinine clearance (Cr(cl)), was reduced by 82% in V, 65 and 61% in the CGS/6.5 and CGS/2.2 groups, and by 69 and 74% in the BZ/6.5 and BZ/2.2 groups, respectively. Both CGS treatments improved the fractional excretion of Na+ (%FE(Na)) significantly from the BZ and V groups. The %FE(Na) for BZ at either dose did not differ from that of V. Elevated urinary cyclic guanosine monophosphate (cGMP), an indicator suggesting increased intrarenal levels of atrial natriuretic peptide (ANP), was observed only in the CGS groups. Histologic examination indicated that BZ/6.5 reduced glomerular sclerosis and the extent of tubular dilation, whereas BZ/2.2 had little effect. CGS, especially at the high dose, virtually normalized the glomerular and tubular pathology. Compared with BZ, CGS 30440 treatment further diminished tubular dilation and proteinaceous cast formation. These tubular effects are consistent with some of the renal actions of ANP. The results from these studies indicate that CGS 30440, a combined ACEI/NEPI, conferred a greater renal protective effect than did ACE inhibition alone.

Diagnosis of experimental encephalitozoonosis in rabbits by complement fixation.

A complement-fixation (CF) test has been developed for detection of experimental encephalitozoonosis in rabbits. The antigen consisted of disrupted homogenates of Encephalitozoon cuniculi spores grown in and released from rabbit choroid plexus tissue culture cells. The test was sensitive and capable of detecting experimental encephalitozoonosis in rabbits as early as 15 days after intracerebral infection. The test was specific for infected animals, and no cross-reactivity was demonstrated between E. cuniculi antigen and Nosema apis, Trypanosoma congolese, Trypanosoma cruzi, rabbit liver powder, rabbit brain powder, and rabbit choroid plexus cell culture. Sera from rabbits infected with Toxoplasma gondii, Eimeria stiedai, and Eimeria perforans did not exhibit antibodies to E. cuniculi. No CF-inhibition activity was detected.

Diagnosis of encephalitozoonosis in experimentally infected rabbits by intradermal and immunofluorescence tests.

The indirect immunofluorescence antibody test was performed on serial blood samples from eight young New Zealand White rabbits with experimental encephalitozoonosis. The test showed seroconversion in six of the eight infected rabbits by the 8th day after inoculation and in all rabbits by the 15th day. Antibody titers reached a peak by about the 36th day after inoculation and remained significantly elevated until the termination of the experiment at 84 days after inoculation. None of four sham-inoculated rabbits showed an immunofluorescence response by the 60th day after inoculation. Immunofluorescence and intradermal test responses were compared before infection and at the 60th day after inoculation in a total of 32 experimentally infected rabbits. Both tests were equally effective (100%) in detecting infected animals. Six of eight (first group) and 22 of 24 (second group) experimentally infected rabbits were confirmed histologically to have lesions compatible with encephalitozoonosis. No cross reactions were observed between Encephalitozoon cuniculi and Toxoplasma gondii, Eimeria perforans, or Eimeria stiedai by intradermal test or immunofluorescence test.