Abstract-In the renin-angiotensin system, renin is known to cleave angiotensinogen to generate angiotensin I, which is the precursor of angiotensin II. Angiotensin II is a vasoactive peptide that plays an important role in blood pressure. On the other hand, the liver is the major organ responsible for the production of angiotensinogen in spontaneously hypertensive rats (SHR). To test the hypothesis that a reduction of angiotensinogen mRNA in the liver by antisense oligodeoxynucleotides (ODNs) may affect both plasma angiotensinogen and angiotensin II levels, as well as blood pressure, we intravenously injected antisense ODNs against rat angiotensinogen coupled to asialoglycoprotein carrier molecules, which serve as an important regulator of liver gene expression, into SHR via the tail vein. The SHR used in the present study were studied at 20 weeks of age and were fed a standard diet throughout the experiment. Plasma angiotensinogen, angiotensin II concentrations, and blood pressure all decreased from the next day until up to 5 days after the injection of antisense ODNs. These concentrations thereafter returned to baseline by 7 days after injection. A reduction in the level of hepatic angiotensinogen mRNA was also observed from the day after injection until 5 days after injection with antisense ODNs. However, in the SHR injected with sense ODNs, plasma angiotensinogen, angiotensin II concentrations, and blood pressure, as well as hepatic angiotensinogen mRNA, did not significantly change throughout the experimental period. Although the exact role of angiotensinogen in hypertension still remains to be clarified, these findings showed that intravenous injection with antisense ODNs against angiotensinogen coupled to asialoglycoprotein carrier molecules targeted to the liver could thus inhibit plasma angiotensinogen levels and, as a result, induce a decrease in blood pressure in SHR. (Hypertension. 1998;31:1166-1170.)

A 69-year-old Japanese female was admitted because of general fatigue. Laboratory data showed elevation of serum total bilirubin, transaminase, gamma-glutamyl transpeptidase, and creatinine levels. An immunological study revealed hypergammaglobulinemia, low titer of complement, and high titers of antinuclear antibody, anti-DNA antibody, and circulating immune complexes. Antibodies to parainfluenza virus 3 were positive. Histology of the liver disclosed numerous giant cell hepatocyte transformations with the lobular architecture being slightly distorted by portal inflammation and fibrosis. These findings led us to make a diagnosis of giant cell hepatitis associated with systemic lupus erythematosus. Prednisolone was effective in improving the anemia and the serum immunoglobulin, immune complex, and antinuclear antibody levels. The addition of cyclosporine to the initial corticosteroid therapy was also beneficial in decreasing the transaminase level and in improving liver histology. The patient died of acute pneumonitis and renal failure on the 166th day after admission. Parainfluenza virus 3 and autoimmune mechanisms were thus considered to be the causes of the giant cell hepatitis.

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In a 29-year-old woman with myasthenia gravis and no visible mediastinal mass, the resected thymus was found to contain a small thymolipoma. Relief of the neuromuscular symptoms followed thymectomy. A very small thymolipoma may be associated with myasthenia gravis even if the content of though thymic tissue is low.

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