Recent progress in hypertension therapy allows us to select appropriate drugs from the large variety of antihypertensive drugs for treating hypertensive patients, once hypertension is diagnosed. Antihypertensive drugs include angiotensin I converting enzyme (ACE) inhibitors, diuretics, calcium entry blockers, P-adrenergic receptor antagonists, a,-adrenergic receptor antagonists, centrally acting a2-adrenergic receptor stimulants, and so forth. It may be said that we are hardly in need of any more drugs against hypertension. Most of these drugs, however, are used for "therapeutic purposes" to suppress the symptoms of hypertension by mitigation of the increased vascular tone. We do not have any prophylactic drugs, since neither the primary cause nor the pathogenesis of essential hypertension has yet been properly identified, despite intensive research on the mechanisms involved in its development.ACE inhibitors are among the most effective antihypertensives. However, studies over a period of years on the genetic and environmental determi-Advancer m Phameculogy, Volume 44 nants of hypertension, lipid abnormalities, and coronary artery disease in Utah in population-based multigenerational pedigrees (Williams et al., 1993) and related investigations revealed that the genetic loci for the structural genes for renin (Williams et al., 1993) and ACE (Jeunemaitre et al., 1992a) and the sodium antiport system (Lifton et al., 1991) were not DNA markers for hypertension.In contrast, segregating single-gene effects were found for several "intermediate phenotypes" associated with hypertension, including intraerythro- Renal Kallikrein-Kinin System in Hypertension I49Although the etiology of essential hypertension is still obscure despite all efforts to identify it, an ongoing series of studies with BN-Ka rats have led us to a reliable hypothesis on the role of the renal kallikrein-kinin system in this condition and also on its role in preventing the development of hypertension in the early stage. This chapter discusses the possible suppressive role of the renal kallikrein-kinin system in hypertension and, on this basis, will propose the novel types of antihypertensive drugs.
SummaryAnalytical results are presented on the chemical composition and other physical properties of a glass, given the identification BNFL-A-S98, made at Pacific Northwest National Laboratory' that is representative of the low-activity waste glass composition proposed by BNFL, Inc? for immobilization of envelope A double-shell tank wastes at the Hanford Site. This glass was prepared for use in a testing program to be conducted at Pacific Northwest National Laboratory and at Argonne National Laboratory for the purpose of characterizing its long-term corrosion behavior. Detailed examination of the glass microstructure using transmission electron microscopy showed structural features indicative of amorphous phase separation. A remelt was performed on a smaller batch (100 g) to ensure rapid cooling. The glass microstructure was reexamined and showed no evidence of phase separation.Selected long-term (some to 860 d) product consistency tests were terminated, and the leachates were analyzed on tests with three other representative low-activity waste glass formulations (L8-1, L8-3, and L8-7). The results showed no evidence of corrosion rate acceleration at three times the duration of tests where another well-studied glass, LD6-5412, had been completely altered under identical test conditions. These tests (and others not discussed in this report) provide clear evidence that low-activity waste glasses with at least 20 mass% Na20 can be made that have excellent long-term corrosion resistance. However, glass composition has a large impact on long-term behavior and so careful experiments with several different techniques are essential to ensuring that a particular glass will have good long-term corrosion resistance.For example, accelerated corrosion tests were performed on the BNFL-A-S98 glass using the pressurized unsaturated flow (PUF) technique at flow rates of 0.5, 1.0, and 2.0 mL/d at 99.5"C. After only 100 to 200 h, effluent pH and electrical conductivity increased sharply, indicating a rapid acceleration in the corrosion rate of the glass. An examination of the reacted glass showed that the grains were covered with a crystalline zeolite precipitate, sodium aluminosilicate hydrate, and a thick amorphous gel layer. Crystallization of the zeolite is thought to be the cause of the observed corrosion rate acceleration because this phase acts as sink for removal of Si and A1 from the aqueous phase, which increases the chemical potential difference between the glass and solution. Measurements of alteration rinds provided an estimate of the glass corrosion rate at between 2 to 5 g/m*-d. This measurement was found to be consistent with corrosion rates calculated from chemical analysis of effluent samples and is near the expected forward rate of reaction for this glass at the test temperature and the estimated pH of pore waters in the PUF tests.A unique combination of PUF equipment and the ultracentrifugation apparatus (UFA) was developed for the quantitative assessment of changes in hydraulic properties (water retention and ...
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