Radionuclide angiography was performed on 41 patients with transmural myocardial infarction (MI) [17 : anterior MI, 24 : inferior MI] and 10 normal subjects in order to evaluate the influence of the infarct site on the global and the regional left ventricular function. The severity of the wall motion abnormality agreed closely with the reduction in the relative regional ejection fraction (%REF). The depression of the left ventricular ejection fraction (LVEF) in anterior MI was greater than that in inferior MI (p<0.01). We also found that the depression of the performance in the infarcted zone in anterior MI was more marked than that in inferior MI (p<0.01). However, function in the noninfacted zone was almost the same in the anterior MI as in the inferior MI. As to the extent of the hypokinetic area, there was no significant difference between the patients with anterior MI and those with inferior MI. The above results indicated that the infarct site is an important determinant of the regional and the global left ventricular function after MI.

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Plasma volume (PV) and extracellular fluid volume (ECF) were determined in 7 patients with essential hypertension (controls) and in 10 patients with primary aldosteronism, while on a high Na diet (342 mEq/day) and on a low Na diet (12 mEq/day). The volume studies were repeated in 6 of the primary aldosteronism patients during treatment with spironolactone for over 3 months. Plasma renin activity (PRA), plasma aldosterone concentration (PAC), cortisol concentration, and serum Na and K concentrations were measured in all patients while o a Na-restricted diet (85 mEq/day) as well as on high-Na and low-Na diets. There were no significant changes in arterial pressure during different Na diets in any groups of patients with essential hypertension, or primary aldosteronism with and without spironolactone therapy. Spironolactone treatment normalized the arterial pressure in batients with primary aldosteronism at all Na intakes. These patients had greater values for PV and ECF than did those with essential hypertension. Spironolactone treatment reduced PV during the low-Na diet, but did not alter it during the high-Na diet. Spironolactone did not produce significant changes in ECF during either the high-Na or low-Na diets. Although there were no changes in PV and ECF in patients with primary aldosteronism due to changes in Na intake, both PV and ECF were significantly less in these patients during spironolactone treatment and in patients with essential hypertension during low-Na intake than during high-Na intake. With primary aldosteronism, PRA was depressed and PAC was elevated when compared to essential hypertension, these were not altered by different Na diets in the patients with primary aldosteronism as they were in those with essential hypertension. During treatment with spironolactone the PRA was restored to normal and showed normal changes with variations in dietary Na, but PAC remained elevated during spironolactone. Plasma cortisol was the same among those with essential hypertension and patients with untreated and spironolactone-treated primary aldosteronism. Serum K was less in untreated primary aldosteronism during all Na diets than in essential hypertensivion, but during spironolactone it was restored to normal. These results suggest that in primary aldosteronism the reduction in arterial pressure by spironolactone treatment does not occur simply by reductions in body fluid volumes. The long-term treatment of patients with primary aldosteronism with spironolactone does not inhibit the production of aldosterone possibly because of enhanced activity of the renin-angiotensin system and an increase in serum K.

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Digoxin was administered orally to eight anemic patients in their anemic and convalescent stages, and serum digoxin concentration was determined by radioimmunoassay. In the anemic patients a significantly lower level of serum digoxin concentration was observed in anemic state compared with convalescent stage at 72 hours after the drug administration (p<0.01). In usual clinical use, a full digoxin effect is expected to be attained as 72 hours. Tritiated digoxin was administered intravenously to anemic and control rats and the tritium in samples of the blood, myocardium and urine were counted in a liquid scintillation counter. The anemic rats showed significantly lower level of serum ³H-digoxin at 6 hours (p<0.01) and lower myocardial concentration at 24 hours (p<0.01). Larger amount of urinary excretion of ³H-digoxin was observed in the anemic rats 6 hours after the drug administration. No significant difference in fecal excretion of ³H-digoxin was found between the anemic and control rats.

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The basic mechanism underlying the abnormal systemic vascular resistance in the spontaneously hypertensive rat (SHR) is poorly understood. To categorize the beta-receptor system in the lungs of these animals, we evaluated receptor number and affinity as an index of this subclass of beta receptors. The lung was chosen because it is not directly affected by the alteration in blood pressure and provides a ready supply of beta-receptors. The aortic blood pressure and heart rate were measured directly through cannulation of the carotid artery. Twenty-four hours later, lung membranes from the SHR and control animals were extracted and partially purified. The affinity and number of receptors were measured by saturation analysis employing ³H-dihydroalprenolol (³H-DHA). Scatchard analysis demonstrated that the number of receptors was identical and of a single class in both sets of animals. However, the beta-receptor from the SHR had a higher affinity than that of normal rats. It is not clear whether this represents an adaptive mechanism following the development of hypertension in the SHR or it represents a basic alteration in this strain of rat. Further studies aimed at categorizing the development of this defect during ontogeny as well as its physiologic consequences should prove valuable in understanding the mechanism of spontaneous hypertension.

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An autopsied patient who had shown typical dilated cardiomyopathy (DCM)-like feature in the end stage of familial obstructive hypertrophic cardiomyopathy (HCM) is presented. The patient, a 38-year-old male, had 2 sisters with HCM. Six years before death, the echocardiogram revealed marked asymmetric septal hypertrophy (ASH) with systolic anterior motion (SAM). The ventricular septum (VS) to left ventricular posterior wall (LVPW) ratio was 19 mm/10 mm and LVEDd was 47 mm. Subsequently, the signs and symptoms of congestive heart failure became progressively worse and DCM-like findings appeared insidiously. Two months before death, the echocardiogram revealed LV dilatation (LVEDd= 55 mm) with diffuse poor contraction, no ASH (VS/LVPW=7 mm/9 mm) and no SAM. At autopsy, the heart weighed 480g and showed dilated LV hypertrophy with normal wall thickness (VS/LVPW = 9 mm/13 mm). Massive fibrosis (30% in the VS), diffuse disarray (18% in the VS) and severe narrowing of the intramural small arteries and arterioles were found in the middle and outer thirds of the VS and the anterior LV wall. The extramural coronary arteries were not stenosed. The insidious progression from HCM to typical DCM-like feature related to the chronic progression of necrosis and massive fibrosis, due to severe stenosis of the intramural coronary artery. The data indicate that patients diagnosed clinically as DCM may be HCM, especially in those with family history of HCM.

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A 61-year-old man with impending myocardial infarction was admitted and treated by percutaneous transluminal coronary recanalization (PTCR) therapy using Urokinase. Patient's symptoms subsided and his general condition maintained stable until the fifth hospital day, when he developed the signs of cardiac rupture. He was operated upon immediately, and the left ventricular rupture was confirmed and repaired successfully. Patient recovered from the surgery well. This report describes the rare successful surgical case of cardiac rupture secondary to acute myocardial infarction in Japan.

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A very sensitive and simplified direct radioimmunoassay system for plasma angiotensin II was developed using the antiserum against synthetic angiotensin II (final dilution = 1:1, 500, 000) in combination with ¹²⁵I-labeled angiotensin II (specific activity = 1, 600μCi/μg). In this assay system, it was possible to carry out a direct assay using 100μl of plasma without any extraction procedure. This conclusion was supported by 100% recovery, parallelism of plasma samples against the standard curve, and no difference in hormone levels, there was also a high positive correlation between the plasma angiotensin II levels measured by this direct assay and the dowex column extraction method. The sensitivity of this assay system was 0.1 pg/tube, which is the highest sensitivity in studies reported to date. The cross-reactivities of angiotensin III and I against this antiserum were 100% and less than 0.1%, respectively, suggesting that the antiserum was very specific for the C-terminal of angiotensin II. Plasma angiotensin II levels in normal subjects after overnight fasting ranged from 3.0 to 21.3 pg/ml (12.0±2.1 pg/ml, mean ±SE). By comparison, plasma angiotensin Ii levels of patients with essentiel hypertension were similar to those in the normal renin group, lower than those in low renin group and higher than those in high renin group. In patients with secondary hypertension, levels were lower in those with primary aldosteronism and higher in those with renovascular hypertension when compared to normal subjects.

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We homogeneously purified human renin substrate from outdated bank plasma and raised antibody against it. The antibody did not cross-react with angiotensin I, angiotensin II or synthetic tetradecapeptide at concentrations of up to 160 n mol, nor did it cross-react with up to 0.2 ml of plasma from rat, rabbit or sheep. it did, however, completely cross-react with human des-angiotensin I renin substrate. A direct radioimmunoassay for human renin substrate was developed using the antibody, and the minimum detectable value of renin substrate found to be 70 pg of protein. Plasma renin substrate concentrations of normal subjects, essential hypertensive patients, diabetic patients and pregnant women were measured by direct and indirect assays. Hypertensive patients had similar concentrations of plasma renin substrate to normal subjects, whereas diabetic patients had significantly lower plasma renin substrate concentrations (p<0.01). The direct assay always (direct assay/ indirect assay) were similar in normal subjects, hypertensive patients, diabetic patients and pregnant women.

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Central cardiovascular effects of the sodium-potassium adenosine triphosphatase (Na⁺, K⁺-ATPase) inhibitor, ouabain, were investigated by injecting it intracerebroventricularly (ICV) using conscious Wistar rats. Ouabain, 0.1-10μg injected ICV, produced does-related pressor responses attaining peak elevations after about 5 min. To investigate the underlying mechanisms of these central pressor responses, angiotensin II blockers were injected ICV before the injections of ouabain. 1-Sar, 8-Ile angiotensin II (ang II a), 50 μg, given 3 min before the ouabain, abolished the pressor responses to ouabain, 5 μg. Angiotensin I converting enzyme inhibitor (CEI, captopril), 100 μg, also significantly attenuated the pressor responses to ouabain. Since previous results with ICV injections of ouabain suggested that the pressor responses are mediated via a release of brain angiotensin II, and the site of action of brain angiotensin Ii is believed to be the anteroventral third ventricle (AV3V) area of the brain, ICV injections of ouabain were repeated using rats whose AV3V areas had been destroyed electrically. The pressor responses were smaller in the AV3V lesioned rats than in sham-operated rats. The abdominal sympathetic nerve activity was recorded using three conscious, normotensive Wistar rats. ICV injections of ouabain, 5μg, elicited pressor responses as described above and these were accompanied by a corresponding increase in the nerve firing, lasting for 5-7 min. These responses were again abolished by pretreatment with an angiotensin Ii antagonist. These results suggest that centrally administered ouabain elicits vaso-pressor responses which increase peripheral sympathetic nerve activity. Because the pressor responses were attenuated both by angiotensin II blockade and AV3V ablation, it is suggested that ouabain release angiotensin II in the AV3V are of the brain, increasing blood pressure.

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Potassium supplementation attenuated the development of hypertension in DOCA-salt rats but did not affect blood pressure in control rats. However, it caused a decrease in body weight in both groups of rats. Sympathetic nerve and pressor responses either to electrical stimulation of the hypothalamus or to intracisternal injections of hypertonic NaCl were enhanced in DOCA-salt rats but were normalized by KCl supplementation. Since the pressor responses to injected norepinephrine or tyramine remained unaltered by KCl treatment, a peripheral inhibition of cardiovascular reactivity was considered unlikely. Pretreatment with methyclothiazide also attenuated the elevation in blood pressure but did not affect the responsiveness to hypothalamic stimulation; hence increased natriuresis or diuresis alone could not account for the effects induced by KCl. These findings are consistent with the conclusion that KCl supplementation attenuates the development of DOCA-salt hypertension in rats by acting on the central nervous system to reduce sympathetic output.

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This study was designed to investigate neurotransmitter release during the sympathetic nerve stimulation of perfused mesenteric arterial beds of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) at young and adult ages. The role of Ca in neurotransmitter release and vascular responsiveness was also examined by using a Ca-antagonist (verapamil). Pressor responses to electrical nerve stimulation and exogenous noradrenaline were greater in SHR than in WKY. Noradrenaline overflow by electrical nerve stimulation from mesenteric arterial beds was also significantly greater in young SHR than age-matched WKY. However, in adult SHR, the noradrenaline overflow was reduced compared with WKY. After verapamil infusion (5.0×10^-7M2.5×10^-6M), suppression of the pressor responses and noradrenaline overflow evoked by electrical nerve stimulation was greater in SHR than in WKY at both ages. The pressor responses to exogenous noradrenaline were also inhibited by verapamil more in young SHR than in young WKY. In adult SHR, the inhibition was similar to age-matched WKY. These results suggest that noradrenaline release from sympathetic nerve endings in SHR increase at a young age and decreases in adults, and depends at least partly on Ca-influx at both ages as dose vascoconstrictor reactivity. Therefore, Ca-dependency in SHR at both pre- and post-synaptic sites of neurotransmission may contribute to the pathogenesis of hypertension.

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We investigated the renin-angiotensin system in the genetically hypertensive (HBP), normotensive (NBP) and low blood pressure (LBP) mice developed by G. Schlager, one of the authors. Renin in the plasma, kidney and submaxillary gland was determined by enzymatic assay and by direct radioimmunoassay (DRIA). Trypsinization of mouse plasma was also investigated. PRA and plasma renin content were not significantly different in the different lines, sexes, and generations. Trypsinization of the plasma revealed the presence of inactive renin, as has also been found in humans, hogs, dogs and rats. The proportion of active renin against trypsinized total renin was about 54-77% and was not significant in the different lines, sexes and generations. There was also no significant difference in renal renin content in the various lines, sexes, and generations. However, in the submaxillary gland, renin content and activity were high in male mice, in every line. These data suggest that the renin-angiotensin system may not contribute to the established phase of blood pressure.

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