Ten mg of Nifedipine, a Ca⁺⁺ antagonist, was administered orally in 2 groups of patients; Group I: 6 patients in hypertensive emergency and Group II: 12 patients with intractable, severe hypertension. Following results were obtained. 1) A marked hypotensive effect was observed in all patients of Group I. The maximum effect was observed within 30 to 60min and lasted for approximately 180min. Clinical symptoms also improved remarkably with the fall in blood pressure. Any side effect was not observed. 2) A marked hypotensive effect was observed in all cases of Group II. The blood pressure fell by 21.4% systclic (p<0.01) and 19.4% diastolic (p<0.02). The peripheral vascular resistance also showed the decrease by 26.2% (p<0.01). The heart rate and cardiac index increased slightly.
It was suggested that the hypotensive mechanism of this preparation is due primarily to the peripheral vasodilatation.

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Urinary excretion of catecholamines, vanillylmandelic acid, and methoxycatecholamines was studied in 50 patients with renovascular hypertension.
The urinary excretion of noradrenaline was increased in patients with elevated peripheral plasma renin activity and in those with elevated renal vein renin ratio in comparison with the patients with normal plasma renin activity.
The urinary excretion of dopamine was diminished and vanillylman-delic acid increased in the entire group of patients with renovascular hypertension.
In the investigated group, following sodium restriction, the mean urinary excretion of noradrenaline increased while dopamine excretion decreased.
These results suggest that the increased sympathetic-activity may play a role in the pathogenesis of renovascular hypertention.

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Two types of the initiation of atrial fibrillation are demonstrated in the continuous recordings of right atrial monophasic action potentials. In the first way, more common, atrial fibrillation takes place suddenly after an extrasystolic atrial beat, in the second one it develops gradually after atrial tachycardia. In the first type the micro reentry starts from the beginning, in the second type only after sustained focal atrial tachycardia.

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The electrocardiogram, phonocardiogram, carotid pulse tracing and apexcardiogram were simultaneously obtained in 25 patients with mitral valve prolapse syndrome and in 62 normal subjects. This allowed us to measure systolic and diastolic time intervals and to construct the apex-carotis diagram (ACD), a new mechanocardiographic method which integrated the catotid pulse tracing and the apexcardiogram in an ortho-gonal coordinate system. In mitral valve prolapse syndrome, the ACD showed curve of the segment of slow ventricular ejection (S-AC) to the right, and a decrease of the field of ventricular ejection. The measur-ment of time intervals gave statistically significant information on Q-I and A2-OS intervals.

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Electrographic changes associated with cyclical reduction of blood flow in partially constricted one or two coronary arteries of anesthetized dogs were examined. In the preparations with single vessel constriction, cyclical ST elevation occurred along with cyclical reduction of coronary blood flow below 25% of the control value. The ST elevation was associated with reciprocal ST depression in the contralateral ventricular surface. In the preparations with double vessel constriction, cyclical reduction of flow frequently occurred in both vessels. The reduction of flow in one vessel occurred not synchronously with that in another vessel in the majority of preparations. The reduction of flow in both vessels was associated with ST elevation in the corresponding areas of the left ventricle. Premature ventricular contractions frequently occurred at the beginning of or immediately after disappearance of ST elevation, or when ST elevation persisted for more than 10min. Ventricular fibrillation frequently occurred in the preparations with double vessel constriction.

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Experimental pulmonary charcoal embolism was produced in dogs. The changes of energy liberation were observed in the right and left ventricular myocardium in relation to the changes of cardiac dynamics. In some dogs, histamine was administered with or without charcoal embolization in order to study whether or not this agent, well-known to be released from lung tissue in pulmonary embolism, had a modifying effect on the myocardial energy metabolism. The effect of histamine was also observed in other dogs. Twice infusions of each 50ml saline suspension of 1Gm charcoal powder were performed into the right ventricle through catheter. The right ventricular overloading was recognized hemodynamically and electrophysiologically. An hour after the first charcoal infusion, mitochondrial fractions were isolated from the right and left ventricles. Uncoupling of oxidative phosphorylation was proved polarographically. These changes were enhanced with histamine (0.01mg/Kg), and were mitigated with diphenhydramine (0.5mg/Kg). Histamine per se was seemed to have a certain uncoupling effect on the heart mitochondria without remarkable alterations in cardiac dynamics and electrophysiologic findings. It was concluded that oxidative phosphorylation of the heart mitochondria was uncoupled in experimental pulmonary charcoal embolism, and that histamine might be a chemical mediator inducing this change by aggravating myocardial hypoxia through pulmonary vasoconstrictive action and/or by affecting the myocardial cell metabolism directly.

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The response of the contractile and the series elastic elements to ethanol was studied isometric contraction and quick release methods after measuring the passive length-tension relationship in glycerinated heart muscle fibers of rats at resting state. In rats consuming 30% ethanol for an average of 5 weeks, maximal developed tension (P₀), the maximal rate of tension development (dp/dt_max) and V_max were significantly depressed, the time to peak tension (t₀) was not changed. As in fresh papillary muscle the modulus of elasticity of active glycerinated muscle increased in proportion to load. The stiffness of the series elastic element showed significant elevation in rats receiving ethanol. The passive stiffness in resting state revealed no significant difference between control and alcohol exposed rats. Therefore, increased stiffness of the series elastic element and diminished contractility are present following chronic alcohol consumption.

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In order to identify the nature of the substance(s) that causes pancreatic edema, pleural effusion, hematocrit increase, and vascular lesion upon administration of renal extracts, effects of a pure preparation of submaxillary gland renin of mouse on blood vessels were studied. This enzyme was administered intraperitoneally to conscious anehpric rats. Blood pressure elevation recorded under unrestricted conditions was proportional to pancreatic edema, pleural effusion, hematolcrit increase, and vascular lesions in small arteries and arterioles. Since the renin administered does not contain any substances and since the function of this enzyme is quite analogous to renal renin, these results have been interpreted to indicate that renin possesses both pressor and permeability activities and that the action of renin alone can account for the vascular lesions and the increased vascular permeability.

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Two cases (1-year-old and 13-year-old) of constrictive pericarditis (CP) associated with atrial septal defect (ASD) are presented. The correct diagnosis was made preoperatively in both cases. Both patients underwent surgery (pericardiectomy and ASD closure). One patient died soon after the surgery because of low caridac output. The other patient was associated with protein-losing enteropathy and it improved dramatically after the operation. Cardiac catheterization is necessary for the diagnosis of this unusual combination. The cause of this unusual combination is obscure.

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Diphenylhydantoin (DPH) and Carbamazepine have been widely used as anticonvulsants and known to have antiarrhythmic properties. Previous reports have shown that arrhythmias such as sinus bradycardia and atrioventricular block can be induced by these agents. In this paper, sinoatrial block (SA block) induced by these agents which were used as anticonvulsants in 3 aged patients is reported.
Three patients, 2 women and 1 man, were over 60 years old. In 2 cases, administration of DPH for recurrent epileptic seizures was followed by SA block. After withdrawal of DPH, SA block disappeared, but resumption of DPH resulted in SA block again. In 1 of these 2 patients, overdrive suppression test revealed normal sinus node recovery time. In the third patient, in addition to DPH which was administered for epileptic seizures, Carbamazepine was given for shoulder pain, then SA block occurred. Withdrawal of these agents restored normal sinus rhythm and combined administration of these 2 agents again induced SA block. Autopsy revealed decreased conduction cells in the sinus node.

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Our detailed study on the physical characteristics of the aorta by using a modified technique confirmed the previous report and showed that the aortic walls of SHRSP were brittle or fragile, obviously thickened and poorly extended, especially in males, in comparison with those of WK throughout their lives. As there is a structural difference between the aortas and the cerebral arteries, the brittleness of aortic walls may not indicate that similar characteristics of cerebral arteries can be a back ground of cerebral lesions.
However, the absorbing function of greater pulse pressure may be less in the aortas of SHRSP because of the reduction of elasticity. Therefore, the cerebral vessels in SHRSP may be exposed to greater pulsatile changes in blood pressure.
This modified method enabled us to record the load-elongation and extension curve of the strips, so that solidity or the stiffness of the aorta would be investigated in the future.

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The functional abnormalities of the cells in the cardiovascular system in SHR were revealed by enzyme histo-cytochemical study. The enzymatic activity was usually increased in the area where the arteries branched and in proliferting cells in the thickened wall. Such was more remarkable in the distorted arteries with aging.
Functional roles of these 4 enzymes were discussed.

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As previously reported (Yamori et al: Jap Heart J 18: 544, 1977) a substrain (A₃) of SHRSP developed no cerebrovascular fat deposition under hypertensive condition when bilateral cervical sympathectomy was performed, and a role of neural vascular control in cerebrovascular atherogenesis was suspected by the fluorescence microscopic study which clarified the morphological features, meshwork or ring-like distribution of the cerebrovascular innervation.
In the present study, for further analysis, the effects of denervation on athero-genesis in the cerebrovascular system of normotensive WK with bilateral carotid arteries ligated was investigated. The denervated group revealed siggnficantly lower susceptibility than the control group. Blood pressure, serum cholesterol level, and gain in body weight showed no significant differences between them. Further, fluorescence microscopic study using Evans blue confirmed the coincidence of the richly innervated vascular segments with increased permeability in the vascular wall.
On the other hand, the present study has proven a difference in the effects of denervation on atherogenesis in the cerebrovascular system in various strains of SHRSP. Denervation was the most effective in A₃ strain and the least effective in A₁-sb. The effect in A₄ strain was intermediate between those in A₃ and A₁-sb. This experimental fact is noteworthy, because A₄ substrain was obtained by crossing between A₃ and A₁-sb substrains.
Furthermore, fluorescence microscopic study of the basilar arteries in SHRSP and WK showed the difference in quality of NA terminal or varicosity between SHRSP and WK, i.e., SHRSP revealed larger NA varicosity. This observation suggested high responsiveness of the densely innervated vascular wall in SHRSP. These results reaffirmed the important role of neural control in cerebrovascular atherogenesis and suggested the involvement of a genetic factor, which is partly due to a difference in neural vascular control.

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Dysfunction of the platelets was proven in SHR by ADP and collagen-induced aggregation, and platelet aggregation in response to collagen extracted from the aorta and mesenteric arteries of SHRSP and SHRSR was also less extensive. The volume distribution of platelets was found to be skewed to larger sizes in SHR, especially in SHRSP, and this finding indicated the possibility of the clinical application of examining the distribution of platelet volume for detecting vascular compli-cations.

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Biomembrane characteristics in stroke-prone SHR (SHRSP) and strokeresistant SHR (SHRSR) were examined using erythrocytes as a simplified model. When erythrocytes were exposed to osmotic stress in the process of the migration from a higher to a lower osmotic gradient by the coil planet centrifugation, erythrocytes from SHRSP were hemolyzed at a higher osmotic pressure than those from SHRSR. Such a difference in biomembrane characteristics may be useful for detecting a genetic disposition of stroke.

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From these results, we can conclude that the developmental pattern of hypertension in the young age is genetically determined and closely related to the incidence of hemorrhage or infarction. These newly selected substrains of SHRSP with higher incidences of cerebral infarction (SP-2) or hemorrhage (SP-1) are regarded as the better models for studying the pathogenesis, treatment, and prevention of infarction or hemorrhage, respectively.

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Acute transient hypertension by norepinephrine was loaded to stroke-resistant (SHRSR), stroke-prone (SHRSP), and normotensive Wistar Kyoto (WK) rats. (SHRSP were most sensitive to norepinephrine in young pre-hypertensive group.) Its effects on cerebral small vessels were studied using Evans Blue to detect the increase of vascular permeability. Severe macroscopic dye-leakages were observed in the areas of "recurrent branching" and "boundary zone", especially among young SHRSP, while SHRSR seemed to be least prone to dye-leakage both in young and adult groups. Among the adults, there was little difference between SHRSP and WK, probably because of the adaptive structural changes of arterial walls in SHRSP caused by long-standing hypertension.

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1) The histopathological abnormalities of the heart tended to be slightly severer in SHRSP with cerebrovascular lesions than those without cerebrovascular lesions. 2) However, SHRSP without cerebrovascular lesions also indicated abnormalities of VCG and histopathological findings. 3) Therefore, cerebral stroke may not directly affect or engender such myocardial lesions. 4) It is still remained to be solved whether the dysfunction of the heart with organic changes may partially contribute to the occurence of cerebral stroke. 5) VCG appeared to correspond to the organic changes of the heart.

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Retinal arterioles never showed sudanophilic rings while the cerebral and mesentric arteries and arterioles rapidly developed clear ring-like fat diposition. (1) Further, it was noteworthy that, in the present study, the precise correlation in "organic" lesions between retinal and cerebral vascular systems was not exactly confirmed. These results suggested a probable difference in the hypertensive involvement of these vascular systems, and substantiated the important role of neural mechanism in the arterial fat deposition, which was a good indicator for the detection of increased vascular permeability, as reported by Horie et al (Jap Heart J 19: 1978). The difference in the innervation of these vessels may be partly responsible for specific susceptibility to arterial lesions, because denervation by superior cervical sympathectomy ameliorated cerebrovascular atherogenesis (Yamori et al: Jap Heart J 18: 544, 1977).

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A typical case of stroke in SHRSP was presented, and respiratory death was confirmed on a polygraphical record. It was also confirmed that the cause of death in stage 4 was lower brainstem damage, which was derived from brain shift and massive brain swelling. On the other hand, the cause of death in stages 2 or 3 was probably due to pneumonia and/or other extracranial accident.

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1) It is generally accepted that the adequate environmental temperature to rear rats is about 23°C, but the adequate temperature that directly contacts to the animal's skin seems to be about 30°C.
2) The blood pressure increased on cold exposure or stimulation. There was a case that the blood pressure increased slightly on hot exposure. This suggests that it is necessary to pay close attention to the condition of warming-up at the indirect measurement of blood pressure.
3) Apoplexy seemed to occur earlier at the low environmental temperature, and the blood pressure seemed to increase also at the high temperature. However, these temperature effects on blood pressure and the incidence of stroke were not so obvious as observed in rearing SP with 0.9% salt solution for drinking.

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1. The diet containing white fish meal or casein as protein source could markedly depress the elevation of blood pressure, prevent the incidence of stroke and elongate the life span in SHRSP. The incidence of stroke in SHRSP was prevented by providing these diets from an early age, the earlier the better. A high content of protein was more effective than a low content, but it seems that there may be an ideal protein content level somewhere.
2. White fish meal, casein, euphausia, beef, and soy bean cake used as protein sources were digested with pepsin in the stomach, and trypsin in the duodenum, and hydrolyzed to amino acids and peptides. It seemed that there were antihypertensive substances in these peptides. These peptides were absorbed and played a role in the slowing of the elevation of blood pressure and the prevention of stroke.

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When chlorella was treated with alkali after decolorization by methyl alcohol and then fractionated by gel filtration, the fraction showed a depressive effect. The blood pressure of SHRSP and SHR showed a fall of an average of 63mmHg 1 hour after intravenous administration, 47mmHg 2 hours after intraperitoneal administration. The blood pressure of normotensive Wistar rats also showed a fall of an average of 32mmHg 1 hour after intravenous administration.

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This study confirmed again that high protein diet feeding decreased the incidence of stroke, and high fish protein diet did attenuate severe hypertension but high soybean protein diet did not affect the hypertension. Dietary amino acid analyses indicated that increases in total amino acids, essential amino acids and nonpolar amino acids but not acid or basic amino acids were significanty related to the reduction of stroke incidence. Among essential amino acids, lysine, threonine, isoleucine, and leucine contents were inversely related to stroke incidence, and methionine content was significantly related to the dietary antihypertensive effect of 626 SPONTANEOUSLY HYPERTENSIVE RAT Jap. Heart J. July, 1978high protein diets. The prophylactic effect of high protein diets may be ascribed to some amino acid constituent.

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In the F₂ generation obtained by the cross breeding between normotensiveVol.19 No.4 SPONTANEOUSLY HYPERTENSIVE RAT 629male WK and hypertensive female substrain of SHRSP (A₁-sb) which had low and high susceptibility to arterial fat deposition, respectively, ring-like fat deposits in the cerebral and mesenteric arteries were observed in high percentage (around 50%). These rats were mostly normotensive (under 150mmHg) and there were no significant differences in blood pressure and serum cholesterol level between rats with and without fat deposition.
These experimental facts suggested that some genetic factors for vascular atherogenesis indifferent to hypertensive genetic factors might be involved in A₁-sb strain of SHRSP and there seems to be a probability for extablishing normotensive atherogenic rats (NAR) by the selective inbreeding of rats from parents which have a high susceptibility to fat deposition and are normotensive. That is, after the development of ring-like fat deposits is confirmed in the cerebral and mesenteric arteries in "normotensive" rats by the BCSS method or by the extirpation of mesenteric arteries, the inbreeding of their descendants is expected to enable us to establish in the near future the new strain which develops fat depositions in cerebral and mesenteric arteries without exception and as yet are normotensive.

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The susceptibility to cerebrovascular fat deposition in prehypertensive SHRSP and SHRSR, with or without unilateral carotid artery ligation, was investigated.
Although no fat deposits were observed in either SHRSP or SHRSR without the carotid ligation, the operated group of SHRSP revealed a significantly higher susceptibility to cerebrovascular fat deposition than the operated SHRSR, qualitatively and quantitatively.
Cerebrovascular fat deposition was regarded as a good indicator for the detection of increased cerebrovascular permeability based on many experimental facts (Yamori et al: Jap Circulat J 39: 601, 1975). Thus, the higher susceptibility to cerebrovascular atherogenesis in prehypertensive SHRSP in comparison with SHRSR suggested that cerebrovascular wall of SHRSP had generically a greater susceptibility to vascular permeability which causes arterionecrosis followed by cerebral breeding or cerebral infarction.
The present study first substantiated a genetical difference, i.e., qualitative and quantitative in vulnerability to cerebrovascular permeability, apart from the heredity of severe hypertension in SHRSP. In addition, the result also suggested the osmotic fragility of erythrocyte membrane might be related to this vulnerability of cerebral arteries and a promising and practical approach for the prescience of cerebrovascular diseases.

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The C-A curves of NA in SHRSP and WKR were modified by aging but those of ACh were not. These results suggest that the modification of receptors by aging may be produced in only adrenaline receptor and the difference observed by the investiagators on the responses to sympathomimetics may be due to the age of rats used.It is clarified that the shift to the right of C-A curve means the decreased affinity (A) and the shift to the downward means the decreased intrinsic activity (IA). A and IA in adrenaline receptor at the ages of 3 and 11M of SHRSP were decreased compared to those of WKR at the same ages. There are some reports that the catecholamine contents in blood of SHRSP was high at the age of 1 to 2M. It may be thought that the increased catechomaine contents in blood influenced on adrenaline receptor and inhibited A and IA, by desensitization and/or the other mechanisms. &-stimulant, oricprenaline showed weaker inhibition against the contractions by the agonists in SHRSP than those in WKR, but dibutyryl C. AMP showed almost the same degree of inhibitory effect on the contractions by the agonists in SHRSP and WKR. These results suggest that the productive activity of C. AMP by &-stimulant may be lower in SHRSP compared to that in WKR. It seems to be coincidance with the previous reports that adenylcyclase activity in SHR-SP was lower than in normotensive rats.Ca antagonist, diltiazem showed the preferential antagonism against the cont-raction by K in SHRSP. It is clarified that the K-induced contraction is induced by only Ca influx, and thus it is thought that Ca influx may be accelerated in SHRSP. The decreased C. AMP productive activity and the increased Ca influx may be the factors of hypertension in SHRSP.

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