MIR, the first available experimental models, are prone to develop ischemic heart disease spontaneously, and they can be regarded as an animal model for scattered-type of myocardial infarction. In this study, histo-pathological examination of MIR which were fed normal diet and died naturally, revealed systemic vascular changes including coronary arteries frequently asso-ciated with thrombosis. These histological findings were also noted in some cases of SHRSP from which MIR was derived, but vascural obstructive changes in general appeared to be dominant in MIR, in which some additional factors related to thrombosis were supposed to be involved. Moreover, alterations in coronary arteries were more marked in MIR than in SHRSP which died mainly from stroke without severe myocardial lesions. Therefore, it can be concluded that MIR is a useful animal model for studying mechanisms and prevention of coronary heart diseases.

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Serum Pi levels in SHRSP were markedly lower in comparison with those in WKY and SHR, while there were no differences in serum Ca levels among these 3 strains at any age of months after birth. Urinary Pi excretion in SHRSP under the condition of established severe hypertension without organic vascular changes (4-6 months after birth) was significantly more and PTH-C levels in SHRSP were significantly higher in comparison with those in SHR. Such higher levels of serum PTH-C seem to be related with lower serum levels and much urinary excretion of Pi, directly and/or indirectly, under the condition of established severe hypertension, in addition to maintenance of serum Ca levels.

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Spontaneously hypertensive rats (SHR), unilaterally nephrectomized, and treated with 30mg/kg streptozotocin (STZ), i.v., showed sustained high blood glucose (>200mg/dl) and pressure (>160mmHg) during 6 to 12-week-observation. Glomerular exudative and medial proliferative changes were seen in the kidney. Thus, an animal model of diabetic nephropathy with hypertension has been established. Moreover, hypertension was not observed in Wistar-Kyoto (WKY) or normal Wistar (WR) rats after STZ treatment. Existance of so-called STZ hypertension in the rat is suspicious.

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These results show that α-hANP relaxed arterial strips but had no effect on pressor responses obtained in perfused mesenteric vessels. These results are similar to those of atripeptin II, a c-terminal deleted form of α-rANP (Kangawa et al.: BIOCH BIOPHYS RES COMN 121: 585-591, 1984) which relaxes rabbit aortic strips but has no effect on perfused rat hind limb vessels (Oshima et al.: CIRC RES 54: 612-616, 1984), suggesting atrial peptides may have little effects on resistance vessels. The difference observed in aged SHR cannot be explained purely on aging because no change was observed in aged WKY. It might be related to changes induced by the hypertensive state of the SHR.

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SHRSP with extremely high blood pressures at an early age were chosen and successive selective brother-sister breeding was conducted while giving apresoline in drinking water at mating. We named these offspring M-SHRSP and succeeded in obtaining an inbred strain. In comparison with SHRSP, the blood pressures of M-SHRSP increased more precociously, their PRA became extremely high, and the incidence of cerebral stroke lesions and hypertensive vascular lesions in the brain, heart, kidnys and testes also became greater at an early stage of life. Various crosses or backcrosses using M-SHRSP, WKY and their hybrids resulted in rat colonies with eight gradients or levels of blood pressure ranging between 135 and 250mmHg. Successive brother-sister breeding in each of these colonies has been continued, resulting in generations 14-17 being close to inbred strains.

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