Angiotensin (AT) II, the bioactive octapeptide in the renin-angiotensin system that plays a key role in cardiovascular homeostasis, exerts its multiple effects through the different types of AT receptors, AT1a, AT1b, and AT2. Previously, we showed chronic hypotension in angiotensinogen (the precursor of AT)-deficient mice and a dramatic increase in renin mRNA levels in its kidney, but it remains unclear which types of AT receptors regulate the blood pressure and renin gene expression. In order to elucidate the physiological roles of AT1a receptor, we generated mutant mice with a targeted replacement of the AT1a receptor loci by the lacZ gene. In the heterozygous mutant mice, the strong lacZ staining was found in the glomerulus and juxtaglomerular apparatus of the renal cortex, which coincided with that of the signals detected by in situ hybridization. Chronic hypotension was observed in the heterozygous and homozygous mutant mice, with 10 and 22 mm Hg lower systolic blood pressure, respectively, than that of wild-type littermates. Both levels of renin mRNA in the kidney and plasma renin activity were markedly increased only in the homozygous mutant mice. These results demonstrated that an AT1a-mediated signal transduction pathway is, at least in part, involved in the regulation of blood pressure and renin gene expression.

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From fractographic observations of specimens that have failed due to rolling contact fatigue, it has been concluded that the first stage of damage is the formation of mode 11 fatigue cracks parallel to the contact surface due to the cyclic shear stress component of the contact stress. Although these initial subsurface cracks, in both metals and ceramics, are produced in a direction parallel to the cyclic shear stress, cracks eventually grow in a direction close to the plane of the maximum tensile stress if we apply a simple mode I1 loading to them. The difference between crack growth in simple mode I1 loading and crack growth due to rolling contact fatigue is, we suppose, whether or not there is a superimposed compressive stress. Based on this hypothesis, we developed an apparatus to obtain the intrinsic characteristics of mode I1 fatigue crack growth, and developed a simplified model of subsurface crack growth due to rolling contact fatigue.Some results in terms of da/dN versus AKII relations have been obtained using this apparatus on specimens of steel and aluminum alloys. Fractographs of the mode I1 fatigue fracture surfaces of the various materials are also provided.

A B S T R A C T Flaking type failure in rolling-contact processes is usually attributed to fatigue-induced subsurface shearing stress caused by the contact loading. Assuming such crack growth is due to mode II loading and that mode I growth is suppressed due to the compressive stress field arising from the contact stress, we developed a new testing apparatus for mode II fatigue crack growth. Although the apparatus is, as a former apparatus was, based on the principle that the static K I mode and the compressive stress parallel to the precrack are superimposed on the mode II loading system, we employ direct loading in the new apparatus. Instead of the simple four-point-shear-loading system used in the former apparatus, a new device for the application of a compressive stress parallel to the pre-crack has been developed. Due to these alterations, mode II cyclic loading tests for hard steels have become possible for arbitrary stress ratios, including fully reversed loading (R = −1); which is the case of rolling-contact fatigue. The test results obtained using the newly developed apparatus on specimens made from bearing steel SUJ2 and also a 0.75% carbon steel, are shown.