Kei Kudo

Sex and age-related differences in the urinary excretion of TXB2 in normal human subjects: a possible pathophysiological role of TXA2 in the aged kidney

Urinary excretion of thromboxane B2 (TXB2), a stable metabolite of TXA2, was measured by radioimmunoassay in 58 normal subjects (17 males and 41 females) aged from 19 to 98 years. The basal level of urinary TXB2 in normal subjects was 100 +/- 6.7 ng/day (mean +/- SEM). In young males, contamination of urine specimens with seminal fluid, which is known to contain large amounts of prostaglandin E, did not change the level of urinary TXB2. Urinary excretion of TXB2 was significantly higher in male subjects than in female (124 +/- 12.6 vs 90 +/- 7.4 ng/day, p less than 0.05). There was no significant age-related difference in 24-h urinary excretion of TXB2 in normal subjects. However, when urinary excretion of TXB2 was expressed as a function of urinary creatinine excretion, it was significantly higher in the elderly (60-93 years old) than in the younger subjects (19-59 years old)(141 +/- 15.7 vs 99 +/- 7.7 ng/g creatinine, p less than 0.02). Renal TXA2 may have a pathophysiological role in the functional impairment of the kidney in elderly people.

Chronic synergistic effect of endothelin-1 and angiotensin II on blood pressure in conscious rats.

We assessed whether there is an interaction between angiotensin II (Ang II) and endothelin-1 (ET-1) in the regulation of blood pressure and sodium and water metabolism in rats. Male Sprague-Dawley rats were divided into four groups. Group I rats received Ang II at a subpressor dose (400 micrograms/kg/day i.p.) for up to 6 days. Group II rats received ET-1 at a subpressor dose (3 micrograms/kg/day i.v.) for up to 6 days. Group III rats received both the subpressor dose of Ang II and the subpressor dose of ET-1. Group IV rats received vehicle only. There was no significant difference in systolic blood pressure (SBP) among groups I, II, and IV during the study. On day 6, SBP in groups I, II, and IV was 148.0 +/- 3.0, 142.7 +/- 2.9, and 143.5 +/- 3.0 mm Hg, respectively. On the other hand, SBP in group III was higher than those of the other groups on day 2 and remained elevated thereafter. On day 6, SBP in group III rats was 189.0 +/- 12.5 mm Hg. There were no significant differences in body weight, fluid intake, urine volume, urinary sodium excretion, or urinary potassium excretion among the four groups. The present results suggest that Ang II and ET-1 exert their pressor effects synergistically and might play a role in controlling blood pressure. They also suggest the possibility of the existence of a common pathway in the hypertension-producing mechanism of these two peptides.

Effects of sodium and angiotensin II on urinary active and inactive kallikrein in rats

To assess possible relationships between sodium balance, angiotensin II (ANG II), and renal active and inactive kallikrein, we studied the effects of sodium loading with 1% NaCl and chronic ANG II infusion (900 micrograms/kg per day) on the urinary excretion of total and active kallikrein for 6 days in conscious rats. We determined urinary total, active and inactive kallikrein by measuring kallikrein activity using a kininogenase assay before and after treatment with trypsin (200 micrograms/ml). Sodium loading produced a sustained increase in urinary total, active and inactive kallikrein excretion. Chronic infusion of ANG II induced a sustained increase in urinary total, active and inactive kallikrein excretion in rats on a regular diet. In rats loaded with sodium, however, ANG II did not induce any further changes in urinary kallikrein excretion. Thus, the present study suggests that both sodium loading and ANG II infusion might stimulate the synthesis of renal kallikrein. In addition, it is suggested that ANG II infusion might stimulate the synthesis of kallikrein, at least partly, via the same mechanism as sodium loading does.

Role of Endogenous Angiotensin II and Prostaglandins in the Antihypertensive Mechanism of Angiotensin Converting Enzyme Inhibitor in Hypertension

The role of endogenous angiotensin II and prostaglandins (PGs) in the antihypertensive effect of converting enzyme inhibitor, captopril, was studied in essential hypertension by the separate and the combined administration of captopril and indomethacin. Although plasma angiotensin II was similarly suppressed by the separate and the combined administration of captopril and indomethacin, captopril lowered and indomethacin increased the mean blood pressure. There were negative correlations between the changes in mean blood pressure and in urinary sodium excretion as well as in urinary PGE excretion. These results suggest that endogenous PGs may be implicated in the antihypertensive effect of captopril through the alteration of sodium balance.

Urinary excretion of TXB2 after angiotensin converting enzyme inhibition in hypertensive patients

Urinary excretion of thromboxane B2 (TXB2), a stable metabolite of thromboxane A2 (TXA2), was measured by radioimmunoassay in 7 essential hypertensive patients before and after a converting enzyme inhibitor, SQ 14225, administration. When a single oral dose of SQ 14225 (50mg) was given to 7 patients with essential hypertension, urinary excretion of TXB2 was increased significantly (from 58.9 +/- 18.1 to 116.1 +/- 20.7 pg/min, mean +/- SE, P less than 0.02) with simultaneous increase in plasma renin activity, urine volume, urinary sodium, urinary potassium and urinary excretion of PGE (from 58.8 +/- 12.8 to 135.1 +/- 30.0 pg/min, mean +/- SE, P less than 0.05). These results indicate that SQ 14225 stimulates vasoconstricting TXA2 production as well as vasodilating PGE production.

Renal Prostaglandin E in the Hypotensive Mechanism of MK-421 in Conscious Rats

To assess the role of renal prostaglandin E in the hypotensive mechanism of MK-421, we evaluated the effects of chronic infusion of MK-421 (6 mg/kg/day i.p.) on systolic blood pressure and urinary prostaglandin E excretion in conscious rats in states of sodium repletion or depletion and also during chronic infusion of norepinephrine (1.8 mg/kg/day i.p.) or vasopressin (7.2 U/kg/day i.p.). The hypotensive effect of MK-421 was greater in sodium depleted than in sodium repleted rats. The hypertensive effect of norepinephrine or vasopressin was inhibited by the simultaneous administration of MK-421. MK-421 induced an increase in the excretion of urinary prostaglandin E, in both sodium repleted and depleted rats. However, simultaneous administration of MK-421 had no influence on the increase in urinary prostaglandin E excretion induced by norepinephrine or vasopressin. In addition, the combined administration of MK-421 with indomethacin (10 mg/kg/day s.c.) still abolished the hypertensive effect of norepinephrine or vasopressin. The disparate effect of MK-421 on urinary prostaglandin E excretion suggests that the renal prostaglandin system is not essential for the mechanism of the hypotensive effect of MK-421.

Increased vascular reactivity induced by essential fatty acid deficiency in rat autoperfused hindquarters

The effects of essential fatty acid deficiency (EFAD) on vascular reactivity to vasoconstrictor stimuli were studied in rat autoperfused hindquarters. Weanling male Sprague-Dawley rats (aged 21 days) were fed diets containing 8% (weight/weight) of stearax plus 2% safflower oil (control diet) or 10% stearax (EFAD diet) for 8 weeks. There was no difference in systemic blood pressure or body weight between the two groups. Basal production of immunoreactive 6-keto-PGF1 alpha by aortic segments was much less in EFAD aortae than in control aortae. In contrast, immunoreactive 6-keto-PGF1 alpha produced by incubating aortic segments with exogenous arachidonic acid (12 mumol/l) was much greater in EFAD aortae than in control aortae. Moreover, conversion of [14C]-arachidonate to [14C]-6-keto-PGF1 alpha was more pronounced in EFAD aortae than in control aortae. Vasoconstrictor responses to noradrenaline (0.01-1.0 mumol/l) and angiotensin II (0.001-1.0 mumol/l) infused into the blood perfused hindquarters were then examined. The rats on the EFAD diet were more sensitive to both noradrenaline and angiotensin II than rats on the control diet (P less than 0.05, two-way ANOVA). Thus, a deficiency of essential fatty acids can lead to increased vascular sensitivity to vasoconstrictor stimuli. Deficiency of arachidonic acid in phospholipid stores is also accompanied by augmented cyclo-oxygenase activity in the vessel wall, similar to that observed previously in spontaneously hypertensive rats (SHR) and rats with one kidney renovascular hypertension.

Endoscopic examination of labial fusion in a postmenopausal woman: a case report

BackgroundLabial fusion is defined as adhesions of the labia minora or majora. Labial fusion may cause urinary retention. Surgical treatment based on an accurate anatomic assessment may be needed, but the usefulness of endoscopic examination for this disease has not been reported.Case presentationA 76-year-old Japanese woman undergoing chemoradiation treatment for esophageal cancer was referred to our department for evaluation of high accumulation in the vagina on a positron emission tomography scan. On physical examination, her labia were noted to be extensively fused with a pinhole opening at the midline. Endoscopic examination revealed that her vagina was filled with urine and there were no abnormalities in her urethral meatus and cervix. The adhesions were separated under anesthesia and there has been no recurrence during follow-up.ConclusionsWe present a case of a postmenopausal patient with labial fusion who underwent successful surgical management. An endoscopic examination enabled us to determine the precise anatomic position and adopt a safe surgical procedure.

The clinical profiles of 78 renovascular hypertensive patients.

昭和50年より当教室で経験した78例の腎血管性高血圧(RVH)について,最近の治療,診断学の進歩を中心に検討を加えた.経皮的血管拡張術(PTA)の導入後,それまでの血行再建術を中心とする治療からPTAを第一選択とする治療法が主流となり,腎摘出術は激減した.アンギオテンシンI変換酵素阻害薬(ACE阻害薬)の登場はRVHの降圧薬に大きな変化をもたらし,それ以前の利尿薬+β遮断薬から利尿薬+ACE阻害薬さらにCa拮抗薬を加えたものに変化し, ACE阻害薬は他降圧薬と併用するとRVHを良好に管理できることが明らかになった.また, ACE阻害薬はRVHのスクリーニングにも有効性を発揮する結果となっている.

Prostaglandins and sodium balance during the reversal of chronic two-kidney, one clip hypertension in rats.

To determine the role of endogenous prostaglandins and sodium balance in the maintenance of high blood pressure in chronic two-kidney, one clip hypertension in rats, we studied the effect of indomethacin infusion on the reversal of hypertension by unclipping. Indomethacin was infused after control measurements, and blood pressure was monitored continuously in conscious rats. Parallel control experiments and sham operations were also performed. Inhibition of prostaglandin synthesis did not affect the postoperative course of blood pressure after the unclipping operation despite the marked decrease of urinary prostaglandin E excretion. The decrease of blood pressure after unclipping was significantly correlated with plasma renin activity prior to unclipping. Sodium balance was not significantly different between the experimental groups. These data indicate no major participation of prostaglandins in the reversal of chronic two-kidney, one clip hypertension, and suggest that the renin angiotensin system participates, at least in part, in the maintenance of high blood pressure in this model of hypertension.