Cardiac output and pulmonary capillary blood flow were measured on 5 normal subjects by dye dilution and N₂O-body plethysmograph method, respectively. To facilitate calculations and to improve signal to noise ratio, a computer of average transient was used. Cardiac output increased from 7.16 ± SEM 0.86 L/min to 8.46 ± 0.72 L/min after the subject changed his posture from upright to supine. Pulmonary capillary blood flow also increased from 5.2 ± 0.44 L/min to 6.95 ± 0.48 L/min. These changes were mostly due to changes in stroke volume. The differences between cardiac output and pulmonary capillary blood flow were 19% and 15% in upright and supine positions, respectively. Conduction time of blood flow pulse from pulmonic valve to pulmonary capillary beds prolonged signifrcantly in supine position. Flow acceleration and pulsatility index did not change by posture. Changes in flow acceleration and changes in PaO₂ were significantly correlated. These results indicate: l) profiles of pulmonary capillary blood flow pulse do not alter by posture except conduction time, 2) zone I which is normally closed because of gravity in upright position seems to recruit in supine position, and 3) blood flow acceleration is responsible at least partially for postural changes in PaO₂.

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In order to study on the morphological factors concerning of the mechanism of appearance of ischemic heart diseases without atherosclerosis, the coronary arteries of the dogs were observed histologically. The following results were obtained . 1 ) Peculiar annular folds were found perpendicular to the blood stream in the main branch of the coronary artery in all 50 adult dogs except 5 young dogs. 2) At the folded portion, the internal elastic lamina was interrupted or deficient and the arrangement of the smooth muscle cells was irregular. 3) The smooth muscle cells of the media at the fold were shrinked to become polygonal after injection of vasopressin and electrical stimulation of the stellate ganglion. 4) There were no findings of atherosclerosis at the folded portion. 5) The folds occurred often at the left circumflex artery. The fact that the internal elastic lamina was interrupted or deficient at the folded portion will be a factor for inducing coronary sclerosis in the future, as a result of increased vascular permeability. Injection of vasopressin into the coronary artery and electrical stimulation of the stellate ganglion induced marked deformity of the smooth muscle cells of the media at the folded portion of the coronary artery. Therefore, it is considered that the existence of the folded portion is related to the increased incidence of local spasm of the coronary artery. The folds were observed mainly at the main branch of the coronary artery, and the location of the folds was exactly in accordance with that of coronary sclerosis and coronary vasospasm in men. From these facts the folds seem to be important as an anatomical factor for the occurrence of ischemic heart diseases.

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Spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) were vectorcardiographically and pathologically studied for myocardial lesions with left ventricular hypertrophy, and findings were compared with those in normotensive Wistar-Kyoto rats (WK). Characteristic vectorcardiogram (VCG) in adult SHR was left superior (posterior) deviation of major QRS portion usually with ST-T changes, which corresponded to the pathological findings such as increased weight of the heart and the left ventricle. In old SHRSP, VCG showed deformity and deviation of QRS loop with prolonged P and QRS durations, and ST-T changes which corresponded to the pathological findings of myocardial degeneration or fibrosis with aggravated left ventricular hypertrophy. Such myocardial lesions were vectorcardiographically followed up in the ageing process and compared with findings in cases of induced, acute myocardial infarction. Vascular or tissue lesions of the brain, the kidney and the heart were clarified to be organ specific and to be related. Vector- or electrocardiogram are parameters for predicting cerebral stroke and/or ischemic heart diseases in humans. Primary prevention and appropriate therapy should be concomitantly considered.

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A 33-year-old woman presented signs and symptoms which suggested mitral stenosis and insufficiency. Subsequent echocardiographic and angiographic testing demonstrated a left atrial tumor which was suspected clinically to be a left atrial myxoma. At surgery, the tumor was partially resected and histological examination revealed that the mass to be a malignant fibrous histiocytoma. At autopsy, the tumor was found to be localized in the heart, and there was no metastasis.

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Our recent findings on molecular weight conversion in the case of renin are summarized and reviewed herein. The molecular weight of renin extracted from isolated renin granules from dogs and rats is approximately 40, 000. This renin reacts with a constituent of kidney extract to form a high molecular weight renin of approximately 60, 000. This constituent was termed a renin binding substance. This substance is probably contained in the cytosol of kidney cortex, and its characteristics are (1) heat instability, (2) non-dialyzability, (3) loss of binding ability by acidification at pH 3.0 and (4) apparent molecular weight is over 47, 000. The binding reaction is mediated in two different ways; thiol oxidation with sodium tetrathionate and exposure of the reaction mixture at 0°C for several days without thiol oxidation.

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The presence or absence of correlation in quantitation of human renin substrate by conventional indirect method (equivalent generated angiotensin I; AI) and newly-developed direct radioimmunoassay (immunoassayable substrate) has allowed us to screen heterogeneity of renin substrate in various pathological states, in conjunction with several procedures for protein analysis . One major peak of substrate activity on polyacrylamide gel electrophoresis (PAGE) was found in normotensive and benign essential hypertensive subjects who gave a 1 : 1 correspondence and a good correlation between two substrate assays. In contrast, certain subjects on estrogen therapy, pregnant woman during the last trimester and some uremic patients demonstrated at least 3 different forms of renin substrate on electrophoresis (R_f of I = 0.65, II = 0.35, III = 0.16). Further analysis by isoelectric focusing PAGE presented additional findings on altered substrate type in patient with Cushing's syndrome (Ip = 4.7 and 4.3). In these additional forms of renin substrate, structural or immunological difference was demonstrated by a lack of binding affinity to antiserum prepared against renin substrate from normotensive subjects. Preliminary data on their AI generation rates in the in vitro incubation with added renin, implied altered kinetic characteristics in the in vivo reninsubstrate reaction. These findings confirm the existence of multiple forms of human renin substrate, which physico-chemical and enzymological properties differ from each other. It is suggested that such proteins may be involved in abnormalities of renin-angiotensin system inducing hypertensive states.

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A 33-year-old woman presented signs and symptoms which suggested mitral stenosis and insufficiency. Subsequent echocardiographic and angiographic testing demonstrated a left atrial tumor which was suspected clinically to be a left atrial myxoma. At surgery, the tumor was partially resected and histological examination revealed that the mass to be a malignant fibrous histiocytoma. At autopsy, the tumor was found to be localized in the heart, and there was no metastasis.

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In order to estimate the modulatory activity of Prostacyclin (PGI₂ ) to the vascular reactivity, pressor responses to angiotensin II (A II) and noradrenaline (NA) and PGI₂ generation of aorta were measured using the rats of sodium loading or of sodium depletion. On the sodium loading, the blood pressure increased gradually and plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were decreased. The pressor responses to A II and NA were enhanced by sodium loading. The PGI₂ generation of aorta was enhanced at the initial stage of sodium loading and decreased thereafter. The increased generation of PGI₂ may represent the adaptive mechanism for the attenuation of the sustained elevation in blood pressure. In sodium depletion, the pressor responses to A II and NA were decreased, and PRA and PAC were elevated. PGI₂ generation of aorta was also increased. These findings suggested that PGI₂ could participate in blood pressure control mechanism on sodium loading and depletion.

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Effects of calcium ionophore, A23187, on prostaglandin E₂ and renin release, and the interrelationship were investigated in anesthetized dogs. PGE₂ concentration in arterial and renal venous plasma was measured by radioimmunoassay, and secretion rate (pg/g·min) from the kidney was calculated. The renin secretion rate (ng/g·min) was calculated simultaneously. Intrarenal infusion of A23187 at a rate of 0.5 mg/min for 2 min resulted in a significant increase in RBF. PGE₂ Secretion rate increased from 61 ± 26 to 1012 ± 566 1 222 ± 500 and 388 ± 125 at 5, 9 and 17 min. Renin secretion rate also increased from 1.4 ± 0.8 to 2.3 ± 1.3, 5.8 ± 2.7 and 5.9 ± 1.6 at 5, 9 and 17 min. However, systemic administration of A23187 at a rate of 0.5 mg/min for 2 min did not alter the parameter. Thus, intrarenal infusion of A23187 affects RBF, renin release and PGE₂ release directly within the kidney. In indomethacin treated dogs (5 mg/kg, i.v.) intrarenal infusion of A231 87 significantly decreased RBF. The renin release with A23187 was also abolished with indomethacin as well as PGE₂ release. These results suggest that calcium mobilization within the kidney plays an important role in PGE₂ Synthesis and release, and that the renal vasodilation and renin release are secondary effects of renal PGs Synthesis and release.

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In order to estimate the modulatory activity of Prostacyclin (PGI₂ ) to the vascular reactivity, pressor responses to angiotensin II (A II) and noradrenaline (NA) and PGI₂ generation of aorta were measured using the rats of sodium loading or of sodium depletion. On the sodium loading, the blood pressure increased gradually and plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were decreased. The pressor responses to A II and NA were enhanced by sodium loading. The PGI₂ generation of aorta was enhanced at the initial stage of sodium loading and decreased thereafter. The increased generation of PGI₂ may represent the adaptive mechanism for the attenuation of the sustained elevation in blood pressure. In sodium depletion, the pressor responses to A II and NA were decreased, and PRA and PAC were elevated. PGI₂ generation of aorta was also increased. These findings suggested that PGI₂ could participate in blood pressure control mechanism on sodium loading and depletion.

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Effects of calcium ionophore, A23187, on prostaglandin E₂ and renin release, and the interrelationship were investigated in anesthetized dogs. PGE₂ concentration in arterial and renal venous plasma was measured by radioimmunoassay, and secretion rate (pg/g·min) from the kidney was calculated. The renin secretion rate (ng/g·min) was calculated simultaneously. Intrarenal infusion of A23187 at a rate of 0.5 mg/min for 2 min resulted in a significant increase in RBF. PGE₂ Secretion rate increased from 61 ± 26 to 1012 ± 566 1 222 ± 500 and 388 ± 125 at 5, 9 and 17 min. Renin secretion rate also increased from 1.4 ± 0.8 to 2.3 ± 1.3, 5.8 ± 2.7 and 5.9 ± 1.6 at 5, 9 and 17 min. However, systemic administration of A23187 at a rate of 0.5 mg/min for 2 min did not alter the parameter. Thus, intrarenal infusion of A23187 affects RBF, renin release and PGE₂ release directly within the kidney. In indomethacin treated dogs (5 mg/kg, i.v.) intrarenal infusion of A231 87 significantly decreased RBF. The renin release with A23187 was also abolished with indomethacin as well as PGE₂ release. These results suggest that calcium mobilization within the kidney plays an important role in PGE₂ Synthesis and release, and that the renal vasodilation and renin release are secondary effects of renal PGs Synthesis and release.

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In order to clarify the relationships among sympathetic nerve, renin-angiotensin and renal kallikrein-kinin systems, and the water-sodium balance in essential hypertension, plasma noradrenaline concentration (pNA), plasma renin activity (PRA), plasma volume (PV), extracellular fluid volume (ECFV), total exchangeable sodium (Nae), urinary kinin excretion, and fractional excretion of sodium (FENa) and of inorganic phosphorus (FEP) were measured during the 4 days immediately after (the first period) and the last 4 days (the last period) of 2 weeks rest following admission with regular diet (Na;256300 mEq/day) in 209 patients with mild essential hypertension. In the first period, the resting level of pNA correlated positively with diastolic blood pressure (p < 0.02), mean arterial pressure (MAP; p < 0.05) and PRA (p < 0.001), and negatively with PV (p < 0.05), ECFV (p < 0.001) and Nae (p < 0.001), respectively. In addition, a significantly inverse correlation was found between MAP and PV (p < 0.01), ECFV (p < 0.01) and Nae (p < 0.01). Following 2 weeks rest after admission, most patients showed a spontaneous blood pressure fall. In 32 patients with MAP reduction more than 5 mmHg (average: 14mmHg), PV (p < 0.001), ECFV (p < 0.01) and Nae (p < 0.001) significantly increased, while FENa (p < 0.001) and FEP (p < 0.0 1 ) decreased after 2 weeks rest. In the last period of 2 weeks rest, no significant correlation was observed between pNA level and MAP, and MAP significantly correlated not negatively but positively with PV (p < 0.02) or Nae (p < 0.05). In all of the values obtained in both the first and the last period of 2 weeks rest, there found significantly positive correlations between pNA and FENa (p < 0.02) and 24-hour urinary excretion of kinin (p < 0.05), respectively. Moreover, urinary excretion of kinin correlated positively with FENa (p < 0.01) and negatively with PV (p < 0.01). However, follwing intravenous infusion of noradrenaline (0.1-0.2 μg/kg/min., 120 minutes), urinary sodium excretion (p < 0.01) and FENa (p < 0.05) significantly decreased and a similar tendency was found in FEP (0.05 < p < 0.1). These findings suggest that an increase of sympathetic nerve activity might be an important mechanism which maintains a high level of blood pressure, particularly, during the first period after admission in patients with mild essential hypertension. In addition, this activity might be closely related to body fluid-sodium balance, and to renin-angiotensin and renal kallikrein-kinin systems. On the other hand, after 2 weeks rest, when the sympathetic nerve activity declined the blood pressure level appeared to be more dependent on body fluid and sodium balance which might be regulated, in part at least, by sodium reabsorption in the renal tubule, including the proximal part, possibly via change in the renal kallikrein-kinin system.

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The role of endogenous prostaglandins in the antihypertensive mechanism of orally active angiotensin I-converting enzyme inhibitor in low renin hypertension was investigated. In the SQ 14225-responders with low renin hypertension, blood pressure was elevated to control level and antihypertensive effect of SQ 14225 was attenuated after the inhibition of endogenous prostaglandin synthesis with indomethacin, while no significant change in blood pressure was found in the SQ 14225-responders with normal renin hypertension. Urinary prostaglandin E excretion was not significantly increased after the SQ 14225 administration but significantly decreased after the administration of indomethacin. There was no significant difference in urinary prostaglandin E excretion between normal renin hypertension and low renin hypertension. These results suggest that SQ 14225 may potentiate extrarenal vasodilating prostaglandin system, probably vascular prostaglandin system, contributing to the antihypertensive mechanism in SQ 14225-responders with low renin hypertension. The augmented renin release following SQ 14225 administration was inhibited by indomethacin, suggesting that endogenous prostaglandin system may contribute to the negative short feedback mechanism of renin release.

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