1. This study was undertaken to examine the possibility that the level of angiotensin-converting enzyme (ACE) increases in vascular tissue, and that this may participate in the pathogenesis of hypertension in spontaneously hypertensive rat (SHR). 2. In SHR, at the established hypertensive stage, the prolonged antihypertensive effect induced by a single oral dose of spirapril was closely correlated to the long-lasting inhibition of ACE in aortae and mesenteric arteries. In contrast, ACE in plasma, lung, heart and kidney recovered from inhibition faster than in vessels. 3. Prolonged daily oral treatment of SHR with spirapril, initiated at the age of 8 weeks and continued for 8 weeks, prevented the development of hypertension with concomitant decrease in aortic ACE activity. Blood pressure continued to be suppressed after the drug was withdrawn, as did the aortic ACE activity. 4. Spontaneously hypertensive rats developed hypertension with age as well as with the increase in aortic ACE activity which became higher with age than that of Wistar-Kyoto (WKY) normotensive control rats. On the contrary, ACE activity in plasma and lung of SHR was substantially lower than that of WKY at any age from 4 to 20 weeks old. Brain ACE activity of SHR did not differ from that of WKY at any age. Aged SHR showed the lower enzyme activity in the kidney compared with that of age-matched WKY. 5. Our results support the hypothesis that increased vascular ACE may play an essential role in the development and maintenance of hypertension in SHR.

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1. The regulation of angiotensin I1 (AII) receptor subtypes was studied in peripheral tissues of 20 week old male spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) rats.2. A11 receptor binding was determined by a quantitative in vitro autoradiography using [125I]-[Sar1,Iles]AII as a ligand on the kidney, adrenal gland, thoracic aorta and heart. CV-11974, a specific AT1 receptor antagonist, and CGP42112B, a specific AT2 antagonist, were used in competition with [125I]-[Sarl,Iles]AII to differentiate AT1 and AT2 receptor binding.3. The relative abundance of each subtype was very similar between SHR and WKY rats. In both strains of rats, the adrenal cortex contained predominantly AT1 receptors, while AT2 receptors predominated in the adrenal medulla. The kidney contained exclusively AT1 receptors over glomeruli, proximal tubules and outer medulla. AT1 receptors were predominant in the thoracic aorta and heart. 4.As for relative receptor density, important differences were observed between SHR and WKY rats. In SHR, the adrenal cortex, outer medulla of the kidney, and heart displayed higher AT1 receptor density than WKY rats. 5.These results indicate that the expression of AT1 receptors is differently regulated in some important targets of A11 in SHR, and suggest that the altered regulation of AT1 receptor presented in this study should be relevant to the pathophysiological features of SHR.

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The increase in urinary catecholamine was observed in the animals subjected to cold (1, 2). Norepine phrine and epinephrine released from sympathetic nervous system and adrenal glands produced to increase plasma glucose and NEFA as fuels. The blockade of catecholamine action and the depletion of tissue cate cholamine led to death during cold-exposure (3). Our previous experiments showed that in the course of prolonged cold-exposure the initial increase in plasma glucose gradually returned to the control level. On the contrary, the increased plasma NEFA was observed to be maintained during cold-exposure. This seemed to indicate that plasma NEFA is a favorable fuel for maintaining the body temperature in pro longed cold-exposure (4).The present experiment was designed to know the changes in colonic temperature, plasma glucose, NEFA and corticosterone in the cold-stressed rats when the hormone sensitive lipase activity was inhibited by 3', 5'-dimethylpyrazole (DMP) and plasma NEFA decreased.Male rats of Wistar strain weighing 200-220 g were used. One hour before cold-exposure, animals were intraperitonealy injected with 20 mg/kg of DMP and subjected to cold of -8°C for 1 .5 hours in a cold room. After cold-exposure animals were decapitated and their blood collected into polyethylene tubes. The collected blood was centrifuged and the obtained plasma was served for the determinations of glucose by the glucose oxidase method, NEFA by the method of Dole (5) and corticosterone by the method of Guillemin et al. (6). Colonic temperature was measured with a clinical thermometer. Statistical analysis of data was done ac cording to the student t-test. Significant differences were given at the level of 5% or less than 5%.The results were shown in Table 1. DMP gave no effects on colonic temperature, plasma glucose and NEFA in the intact rats except the significant increase in plasma corticosterone. The increase in plasma NEFA by cold-exposure was significantly inhibited in the DMP treated rats compared to the control group. On the contrary, the significant increase in plasma glucose was found in the DMP treated rats with cold exposure. The increase in plasma corticosterone was small in the DMP treated plus cold-stressed rats and the corticosterone level was about the same in both the intact and DMP treated animals subjected to cold.

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