Tatsuo Shinagawa

Human decidua is a major source of renin.

Plasma prorenin levels are elevated in normal pregnant women. Current evidence suggests renin production by tissues of the uteroplacental unit contribute to this elevation. The purpose of this investigation was to define the source of renin biosynthesis within the human uteroplacental unit and to characterize the renin produced. RNA extraction and Northern blot analysis consistently demonstrated renin mRNA expression in uterine lining both in the pregnant (decidua) and nonpregnant states (endometrium) and in fetal chorion laeve, which is inseparable from the decidua. In contrast, renin mRNA expression was not detected in basal plate and intertwin chorion (which is separate from decidua), amnion, myometrium, or placental villi. The total renin content in decidual homogenates was two- to threefold greater than in endometrial homogenates, and cultured human decidual cells produced significantly more total renin than cultured human endometrial cells, suggesting that pregnancy enhanced renin production by the cells lining the uterus. Immunoblot analysis and [3H]leucine incorporation identified 47,000-mol wt prorenin as the major form of renin produced by cultured human decidual cells. These studies indicate that maternal decidua is the major source of prorenin in the uteroplacental unit.

Extrarenal renin-secreting tumors : insights into hypertension and ovarian renin production

Although renin-secreting tumors are rare, they must be considered in the differential diagnosis of hypertension associated with hypokalemia, which occurs commonly in the hypertensive population. The finding of an ovarian renin-secreting tumor emphasizes the potential importance of the ovary as an extrarenal source of renin; the local ovarian renin-angiotensin system may play a key role in reproductive function by regulating vascular reactivity, local blood flow, steroidogenesis and other physiologic effects. In the illustrative case presented, a renin-secreting ovarian leiomyosarcoma was obtained from a women who presented with hypertension and hypokalemia. Plasma prorenin levels were markedly elevated. Tumor excision was quickly followed by a fall in prorenin levels and tumor recurrence was accompanied by an increase in prorenin levels. Active renin concentration in the tumor homogenates was similar to that found in kidney homogenates while the tissue prorenin concentration was approximately 20 times that found in kidney tissue. When cultured for up to 4 weeks, ovarian tumor cells secreted greater than 95% prorenin. Immunoblot analysis demonstrated that tumor renin had a molecular weight of 47,000, similar to that of human recombinant prorenin. Immunohistochemical staining of tumor tissue with antibodies against human renal renin at the electron microscopic level demonstrated the presence of renin primarily in membrane-bound vesicles and rarely in dense-core secretory granules. These findings suggest that prorenin in this ovarian tumor was secreted by the constitutive pathway, which is mediated by these amorphous vesicles.

Prompt and Long-term Prophylactic Effect of Closed Loop Stimulation against Paroxysmal Atrial Fibrillation in a Patient with Sick Sinus Syndrome

A 72‐year‐old woman with sick sinus syndrome (SSS), who had frequent paroxysmal atrial fibrillations (PAfs) and normal cardiac function, was admitted to our hospital due to syncope. PAfs frequently occurred during the first week after DDD pacemaker implantation (PMI), with closed loop stimulation (CLS) rate‐adaptive mode off, but were completely suppressed during the second week, with CLS on, and had been well‐controlled over three years thereafter. However, PAfs occasionally occurred under intense sympathetic activity during 6 months after PMI as well, and were effectively terminated by disopyramide which had anticholinergic effect. Thus, the development and maintenance of PAf were thought to be associated with destabilized cardiac autonomic activities, that is, sympathetic and parasympathetic dominance, respectively. Additionally, heart rate variability analyses after implementation of CLS revealed the restoration of sympathetic and parasympathetic components. Accordingly, CLS mode was considered to play a critical role in preventing PAf by reflecting autonomic activity in heart rhythm in this SSS patient.

Importance of Mitral Regurgitation After Isoproterenol Infusion in the Aged

老年者非リウマチ性僧帽弁閉鎖不全症 (MR) 23例 (54歳～90歳, 平均77.8歳) に於て収縮期雑音, 僧帽弁逆流量, 心拍出量等に対するイソプロテレノール (ISP) の効果を検討し, 老年者MRの僧帽弁支持機構不全を中心に考察を加えた.ISPによる収縮後期雑音減少群では16例, 非減少群は7例であった. 収縮期雑音の強さは減少群平均 Levine 2.7°で非減少群2.4に比して弱くなく, 一方心不全は減少群でやや軽度であった. 心胸比は差がなく, 減少群では心筋梗塞7例 (43.7%), 非減少群では0%と心筋梗塞が多く見られた. 色素稀釈法による僧帽弁逆流量は減少群で48.9%, 非減少群で76.4%であった. ISPによる変化では心拍出量増大は減少群で大であった. 心エコー図と色素稀釈法より推定した僧帽弁逆流量も非減少群44.1ml, 減少群28.4mlと減少群で少なかった.以上老年者MRの中にはISPによる心筋収縮力増強により僧帽弁支持機構不全の改善により僧帽弁逆流を減少させうる症例を認めた. 一方, 心不全の軽快や心拡大の減少と共に収縮期雑音減少を示す症例も認められ, MRの発生機序として左室収縮力の障害も一因と考えられた.