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Biomedical subjects

N Ohara

Publications and source records attributed to N Ohara.

At least 217 records · Page 12Linked to original sources

Effect of an antianginal drug, perhexiline, on myocardial oxygen consumption in anesthetized open-chest dogs compared with verapamil and glyceryl trinitrate.

A pharmacological study on myocardial oxygen consumption was carried out in open-chest dogs using an arterio-venous oxygen difference analyzer. The continuous monitoring of the oxygen difference showed that the peak changes in coronary blood flow did not coincide with the greatest change in myocardial oxygen consumption. Perhexiline, 0.3-3 mg/kg intravenously, increased coronary blood flow and decreased myocardial oxygen consumption, dose-dependently. Perhexiline decreased aortic and systemic blood pressures and left ventricular work except for lower doses of perhexiline which slightly increased cardiac output and ventricular work. Over-all mechanical efficiency of the left ventricle was increased with perhexiline, while the efficiency was decreased around the peak effect of larger doses of the drug on systemic blood pressure and coronary artery. Verapamil, 0.03-0.3 mg/kg, showed essentially the same effects as perhexiline with ten-fold potency superior to perhexiline. Glyceryl trinitrate showed inconsistent effects on coronary flow and myocardial oxygen consumption, and it decreased cardiac work and mechanical efficiency of the left ventricle.

Animals↗

Different effects of captopril on blood pressure in the acute and chronic two-kidney Goldblatt hypertensive dogs.

Captopril was administered to acute (8 to 14 days after unilateral renal artery constriction) and chronic (71 to 127 days after the constriction) two-kidney Goldblatt hypertensive dogs, and to normotensive ones for 21 days (oral administration of 10, 20 and 40 mg/kg/day, consecutively each 7-day period). The decrease of arterial blood pressure was remarkable in hypertensive animals with high plasma renin activity, but not in the normotensive animals. In the acute stage of hypertension, the antihypertensive effect of captopril was dose-dependent and persistent even after its cessation. In the chronic stage of hypertension, blood pressure also decreased, but the response was not dose-dependent and did not continue after cessation. Plasma renin activity rose in both hypertensive and normotensive animals during the treatment with captopril. There were no significant changes in heart rate, daily urinary volume, sodium balance, and renal clearances of sodium (CNa), potassium (CK), chloride (CCl) and creatinine (CCr). Circulating blood volume was also not altered. These results indicate that the main mechanism of antihypertensive effect of captopril in two-kidney Goldblatt hypertensive dogs is an inhibition of the angiotensin converting enzyme. In addition, the different effects in the acute and chronic hypertensive dogs suggest that some differences exist in the mechanism(s) of maintaining blood pressure between the two stages of two-kidney Goldblatt hypertension in dogs.

Administration, Oral↗

Analysis of the mechanism of acute decrease of blood pressure induced by captopril (SQ 14,225) in dogs by the use of aprotinin, SAR1-ILE8-angiotensin II and indomethacin.

Acute effects of captopril (SQ 14 225) on blood pressure were investigated in pentobarbital anesthetized dogs. Intravenous captopril (0.1-3 mg/kg) caused reduction of blood pressure dose-independently, while dose-dependent attenuation of exogenous angiotensin I-induced pressor response and potentiation of bradykinin-induced reduction of blood pressure were observed wih the same doses of this agent. This acute decrease in blood pressure was partially inhibited by a pretreatment with any one of aprotinin, Sar1-Ile-8-angiotensin II and indomethacin. More significant inhibition of the blood pressure decrease was observed after the combined pretreatment with Sar1-Ile8-angiotensin II and indomethacin or that with all the three drugs, though no complete abolition of the blood pressure decrease was achieved. These results suggest that captopril may decrease blood pressure in anesthetized dogs through other mechanism(s) in addition to angiotensin converting enzyme inhibition, including the prostaglandin release probably from the kidney.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Determination of captopril in biological fluids by gas-liquid chromatography.

The quantitation of captopril in biological fluids by gas-liquid chromatography using a flame photometric detector is described. Captopril was converted into an adduct with N-ethylmaleimide and then into the hexafluoroisopropyl ester. The latter derivative was separated on a 2% OV-210 column and determined by employing the captopril-N-hexylmaleimide adduct as an internal standard. The blood level and urinary excretion of captopril administered intravenously to dogs were measured by the proposed method.

Animals↗

Sex steroidal regulation of uterine leiomyoma growth and apoptosis.

Uterine leiomyomas develop during the reproductive years and regress after menopause, indicating ovarian steroid-dependent growth potential. Although the clinical and biochemical observations have traditionally supported an important role for estrogen in the promotion of leiomyoma growth, there is also increasing evidence to suggest the involvement of progesterone in the pathogenesis of leiomyoma. In this review, much attention has been paid to characterizing the molecular mechanisms of sex steroidal regulation of leiomyoma growth and apoptosis by evaluating the effects of sex steroids on the expression of growth factors and apoptosis-related factors. The effects of GnRH agonist on the expression of these factors in leiomyoma are also described. 17beta-Estradiol up-regulates epidermal growth factor (EGF) receptor, but down-regulates p53 protein in leiomyoma cells, whereas progesterone augments EGF and Bcl-2 protein, but inhibits insulin-like growth factor (IGF-I) and tumour necrosis factor (TNFalpha). Since it is now evident that EGF and IGF-I act as local factors which stimulate leiomyoma growth, these findings suggest that progesterone may have dual actions, stimulatory and inhibitory, on leiomyoma cell growth and survival, depending on the local growth factor conditions around each leiomyoma. This may explain why the size of uterine leiomyomas during the use of levonorgestrel-releasing intrauterine system (LNG-IUS) increases in some but decreases in other instances. This may also explain why the size of leiomyomas during pregnancy does not increase despite the overwhelming increase in circulating concentrations of sex steroid hormones. Moreover, there is further evidence to suggest that the interactions between estrogen receptors and progesterone receptors may be involved in the modulation of gene transcription activity in leiomyoma. This review demonstrates that leiomyoma growth is integrally regulated by the complex cross-talk between sex steroid hormones and growth factors.

Animals↗

Invasive adenocarcinoma arising from uterine adenomyosis involving the rectosigmoid colon.

We describe a rare case of invasive endometrioid adenocarcinoma arising from uterine adenomyosis involving the rectosigmoid colon. At laparotomy the uterus was densely adherent to the rectosigmoid colon. The final pathologic study of surgical specimens revealed intact endometrium and endometrioid adenocarcinoma scattered diffusely throughout the posterior myometrium with direct invasion into the rectosigmoid colon. There were numerous adenomyotic foci around the carcinoma. This case emphasizes the fact that biopsy findings from a uterus with adenocarcinoma arising from adenomyosis can be false negative. Physicians should keep in mind the possible existence of malignancies arising from adenomyosis when uterine malignancies are clinically suspected but histologic evaluation fails to confirm the diagnosis.

Aged↗