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The cerebrovascular permeability quantitatively determined by the retention of 131I-human albumin in the perfused brains was increased in SHR, especially in stroke-prone SHR compared with normotensive Wistar-Kyoto, and confirmed the macroscopical or microscopical findings on the leakage into the brain or trypan blue or peroxidase injected intravenously 2 to 3 hours before sacrifice. The localization of increased vascular permeability in SHR corresponded to the predilection sites of cerebral hemorrhage or softening, which developed likely following the increased cerebrovascular permeability.

The hypothesis that plasma renin is a major risk factor in the development of cardiovascular complications of hypertension was evaluated in a model animal, the spontaneously hypertensive rat (SHR). Plasma renin levels and pathological findings were studied in stroke-prone and -resistant strains of SHR at various ages. The stroke-prone strain showed significantly higher plasma renin levels at and after seven months of age, while the stroke-resistant strain showed no significant differences from the control at any age. High plasma renin levels were always associated with evident vascular complications in the kidney and the brain, indicating underlying angionecrosis and malignant transformation of hypertension. However, no evidence indicated that a higher plasma renin preceded the development of vascular lesions. Thus the high plasma renin would be a result rather than the cause of hypertensive vascular lesions.

The selectively-bred substrains of spontaneously hypertensive rats with a greater vulnerability to vascular lesions rapidly developed arterial fat deposition within 1 or 2 weeks as well as a greater hypercholesterolemic response when fed on high fat cholesterol diet including 20% of suet, 5% of cholesterol and 2% of cholic acid. The ring-like arterial fat deposition at the branches of superior mesenteric arteries and cerebrobasal arteries, which was found to be good indices for the deposition of intrarenal or coronary arteries, was not observed in normotensive rats fed on high fat cholesterol diet for 3 months, greatly delayed in SHR under antihypertensive treatment and accelerated by 1% salt loading in drinking water. The horseradish peroxidase infused intravenously 1 to 4 hours before sacrifice leaked in ring-like forms which corresponded to the fat deposit in mesenteric arteries. The incorporation of 3H-proline infused 4 hours before sacrifice was enhanced in the mesenteric arteries with the fat deposition. These results clearly indicated that hypertension was a great contributory factor to rapid arterial fat deposition, which was caused by an increased vascular permeability and enhanced the arterial collagen formation, the initiation process of arterio- or atherosclerosis.

In rats treated with DOCA plus high salt or with high salt alone, hypertensive rats with renal vascular lesions showed an incomplete suppression of KRA. Cathepsin activity of rat kidney was higher under high salt loading than in the control. Beta-glucuronidase activity was greatest in rats with renal vascular lesions and smallest in rats fed on normal chow. RNase and DNase activities were greater in rats with renal vascular lesions than in rats without renal vascular lesions under high salt loading. 2) In rats of both sexes SHR showed greater KRA and cathepsin activities than WK rat under high salt loading. In female rats DNase, RNase and beta-GPase activities were greater in SHR than in WK rat under high salt loading. 3) KRA was higher in SHRSP aged 10 months than in SHRSR, though KRA of SHR was smaller than KRA of WK rat. Cathepsin activity was greater in SHRSP than in SHRSR. DNase and beta-NAGA activities were greater in SHR than in WK rat. 4) In 7 weeks of age SHRSR showed more PRC than SHRSP. At the age of 10 months SHRSP showed higher PRC than WK rat. The roles renin and lysosomal enzymes in hypertensive renal vascular lesions were discussed to some extent.

The offspring of male stroke-prone SHR, 80 in total, were divided into treated and nontreated groups at the age of 30 to 45 days. The former groups were treated with alpha-methyl dopa (2 g/l in the drinking water), or L-dopa (2 g/l) with or without peripheral decarboxylase inhibitor (MK-486, 1-3 g/l) or apresoline (0.08 g/l) thereafter till they died a natural death during 1 and a half year observation period. So far as hypertension was controlled under about 210 mmHg, no stroke was observed, while nontreated group developed cerebrovascular lesions spontaneously in about 80 per cent. This study experimentally confirmed the importance of blood pressure control for the prevention of stroke.

In an attempt to study whether TSH abnormality was genetically determined in SHR and SPR, plasma T4, T3, TSH and prolactin concentrations were measured in the animals with intervals of 1 to 3 months. Hypertension was found in 6-month-old SHR and SPR, but it was not found in younger animals. In contrast, a decrease of plasma T3 and an increase of plasma TSH were found in 15-day-old SHR. Also, an increase of TSH was found in 1-month-old SPR in spite of normal plasma T3 concentration. These abnormalities in SHR and SPR increased progressively with age. It is suggested that thyroid-pituitary abnormality was genetically determined in SHR and SPR.

Thyroid activity was tested in two substrains of SHR. Plasma level and pituitary content of TSH increased significantly in both substrains of SHR. As a result, the thyroid weight and thyroidal radioiodine uptake increased significantly. Plasma T3 concentration was decreased in Kyoto substrain but was normal in NN substrain, while plasma T4 concentration decreased significantly in both substrains. Since the pituitary content and plasma level of TSH were significantly higher in spite of the normal concentration of plasma T3, it is concluded that the pituitary "hormostat" is set at a higher level at least in the NN substrain of SHR.