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Low doses (10(-16)-10(-10) M) of endothelin-3 (ET-3) elicited continuous vasodilations of mesenteric arteries preconstricted with norepinephrine (NE) but not with KCl. In arteries perfused with Ca2+ free solution, ET-3 did not affect the perfusion pressure. In endothelium-denuded arteries preconstricted with NE, ET-3 significantly elevated the perfusion pressure in a dose-related manner. The levels of cyclic GMP and cyclic AMP from the intact arteries were significantly elevated by ET-3; the cyclic GMP elevasion disappeared with methylene blue. Following endothelium-denudation, cyclic GMP elevation was abolished, but cyclic AMP elevation was unaffected. Levels of 6-Keto-PGF1 alpha in the arteries were not changed appreciably by ET-3. These data indicate that the vasodilating effects of ET-3 depend on the presence of extracellular Ca2+ and the existence of endothelium. They are accompanied by elevations of cyclic nucleotides and the elevation of cyclic GMP depends on the endothelium. It is possible that the vasodilating effects of low doses of ET-3 are associated with endothelium-derived relaxing factor.

It has been demonstrated that the adenylate cyclase activity of vascular smooth muscle regulates its tonus. The present study was undertaken to examine adenylate cyclase activity in early and established deoxycorticosterone acetate (DOCA)/salt hypertensive rats. Early and established DOCA/salt hypertensive rats were prepared by injecting 30 mg of DOCA weekly for 3 and 10 weeks, respectively, into male Wistar rats given drinking water with l% saline. The membrane protein fraction of the aorta was obtained by centrifugation at 37, 000 g. To the incubation medium containing the protein, 50μM isoproterenol, 100μM GTP, 50μM forskolin or 25μM calmodulin was applied. The adenylate cyclase activity was determined by a modified method developed in our laboratory using double. isotope counting. The adenylate cyclase activity in the early DOCA/salt hypertensive rats was significantly higher (p < 0.05) than that in the control rats in the basal condition, which was unaffected by additions of isoproterenol, GTP or forskolin. There was no significant difference in basal adenylate cyclase activity between the established DOCA/salt hypertensive and control rats. The adenylate cyclase activities in the established DOCA/salt hypertensive rats were significantly lower with GTP (p < 0.02) and forskolin (p < 0.01) as compared with the control rats. Calmodulin elevated the adenylate cyclase activity significantly (p < 0.05) in the established DOCA/salt hypertensive rats as well as in the control rats. However, enzyme activity with calmodulin in the established DOCA/salt hypertensive rats was significantly lower (p < 0.05) than that in the control rats. These results suggest that the adenylate cyclase activity of vascular smooth muscle in early DOCA/salt hypertension was fully stimulated in the basal condition, and that there was an abnormality distal to the β-adrenoceptor, especially the catalytic subunit of the adenylate cyclase in established DOCA/ salt hypertension. Accordingly, it is thought that reduction of the enzyme activity may be attributable in part, to biochemical events involved in the pathogenesis of DOCA/salt hypertension.

We examined the effect of angiotensin I (AI), without the effect of angiotensin II (AII) converted from AI, on the weight of the adrenal glands, adrenal corticosterone (B) and adrenal aldosterone under conditions where the renin-angiotensin system was suppressed, since a reduction in the size of the adrenal glands is often observed in DOCA/salt hypertensive rats. Sixty male Wistar rats fed on a 1% NaCl solution were divided into 6 groups as follows: a) Salt group: received sesame oil and vehicle, b) Salt + C group: received sesame oil and MK422 (0.14 mg/day), an angiotensin converting enzyme inhibitor (CEI), c) DOCA group: received DOCA (30 mg/week) and vehicle, d) DOCA + A group: received DOCA and AI (0.5 mg/kg/day), e) DOCA + A + C group: received DOCA and AI with MK422, and f) DOCA + C group: received DOCA and MK422. After 4 weeks, the rats were sacrificed to sample their blood and remove their adrenal glands. There was no significant difference in adrenal B among the groups apart from the DOCA + C group. Adrenal aldosterone was lower in the groups of DOCA/salt hypertensive rats than in the Salt group and Salt + C group. Furthermore, the DOCA + A + C group and DOCA + C group had lower adrenal aldosterone levels than the DOCA group and DOCA + A group.(ABSTRACT TRUNCATED AT 250 WORDS)

We investigated the basal levels and responses of cyclic GMP (cGMP) derived from perfused mesenteric arteries to acetylcholine (ACh) and sodium nitroprusside (SNP) in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) at different ages, in order to evaluate the basal and stimulated release of endothelium-derived relaxing factor (EDRF) from the resistance vessel during the development of hypertension. The mesenteric arteries were removed from 8-, 12- and 20-week-old WKY and SHR, and were perfused with Krebs-Henseleit solution containing 0.2 mM isobutyl methyl xanthine. The effluents from the perfused arteries were corrected before and after infusions of graded doses of ACh or SNP, and the levels of cGMP were measured. The basal levels of cGMP from the msenteric arteries in the 12- and 20-week-old SHR were significantly lower than those in age-matched WKY. A negative correlation was observed between the basal levels of cGMP and the systolic blood pressure in SHR, but not in WKY, among all ages. On the other hand, there were no differences in the responses of cGMP to infusion of ACh between the WKY and SHR at each age. Moreover, the responsiveness of cGMP to in-fusion of SNP in the 12-week-old SHR was much higher than that in age-matched WKY. These data suggest that the basal cGMP formation in the arteries which may reflect the basal release of EDRF is reduced in older SHR and is associated with the development of hypertension, and that the stimulated ralease of EDRF is not associated with the development of hypertension.

症例は21才男性.減量を目的に6カ月間に約50kg体重を減少させ,全身倦怠感,意識消失発作を来したため入院となった.入院時,心電図上心拍数36回/分の洞性徐脈を認め,心エコーでは心膜液貯留を認めた.また頭部CTスキャンでは脳萎縮を認めた.血液検査では甲状腺機能検査においてlow T3 syndromeを呈し,さらに経過中, GH値の高値,一過性のGOT, GPT値の上昇等を認めた.本症例は著しい体重減少をきたしているものの,入院時,標準体重を示していることから,我国における神経性食欲不振症の診断基準にあてはまらないが,臨床経過等を総括すると,多彩な臨床症状を呈した神経性食欲不振症の男性例と考えられた.

In the present study, the pressor activity of 19-hydroxyandrostenedione (19-OH-AD) (which is a kind of androgen) and the presence or absence of the possibility of its role as an amplifier of mineralocorticoid were investigated. 34 Wistar rats of 8 weeks of age were used as the experimental subjects. The rats were divided into 3 groups, the control group (n = 12), 19-OH-AD group (n = 12) and DOCA group (n = 10). The control group was given 0.2 ml of sesame oil, the 19-OH-AD group was given 10 mg of 19-OH-AD dissolved in 0.2 ml of sesame oil, and the DOCA group was given 10 mg of DOCA dissolved in 0.2 ml of sesame oil. This was subcutaneously administered three times a week for 4 weeks, and body weight and blood pressure were observed. At the termination of the experiment, blood was sampled by decapitation, and the serum sodium concentration, erythrocyte sodium content, plasma renin activity (PRA), plasma atrial natriuretic hormone (alpha-rANP), and contents of DOC, corticosterone and aldosterone in adrenal gland were determined. The following results were obtained. The blood pressure at the termination of the experiment was higher than that at the initiation of the experiment by 9.9 +/- 1.9 (S.E.), 31.3 +/- 1.7, and 46.2 +/- 2.0 mmHg in the control, 19-OH-AD and DOCA groups, respectively, where significant elevations were observed in both the 19-OH-AD and DOCA groups as compared with the control group. As to the serum sodium concentration, only the DOCA group showed a significant elevation (p less than 0.001) as compared with the other two groups. However, the erythrocyte sodium contents of both the 19-OH-AD and DOCA groups increased significantly as compared with the control group. Moreover, the increase of the DOCA group was significantly higher (p less than 0.001) than that of the 19-OH-AD, and a significant positive correlation between the elevation of blood pressure and the erythrocyte sodium content was observed (p less than 0.001). As to the PRA value, only the DOCA group showed a significant lowering as compared with the other two groups, whereas alpha-rANP value of the DOCA group showed a significant elevation as compared with the other two groups. As to the contents of steroid hormones in the adrenal gland, all of the steroid hormones were significantly lower in the DOCA group, while those of the 19-OH-AD group were unchanged as were those of the control group.(ABSTRACT TRUNCATED AT 400 WORDS)