Incidence of stroke and acute myocardial infarction in subtropical islands, Okinawa, Japan.
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Biomedical subjects
Publications and source records attributed to K Fukiyama.
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1. We investigated a link between sympathetic nervous function and carbohydrate metabolism by measuring renal sympathetic nerve activity in response to intravenous load of glucose in alpha-chloralose-urethane anaesthetized rabbits. 2. Intravenous infusion of a 25% glucose solution (0.5 g/kg) over 3 min caused a transient increase in arterial blood pressure and a decrease in renal sympathetic nerve activity. Thereafter, these parameters were restored and remained around preload levels while plasma glucose and insulin concentrations were still elevated. 3. Equimolar mannitol solution produced similar patterns of change in blood pressure and nerve activity without an elevation of plasma glucose and insulin levels. 4. The transient changes in blood pressure and renal nerve activity could be attributed to acute hypervolaemia indicated by similar changes in plasma osmolality and haematocrits in the two groups of treatment. 5. The present study did not support a close relationship between carbohydrate metabolism and the sympathetic nervous system regulating cardiovascular function.
Severe hypertension developed in a fifty-five year-old woman after surgical removal of a retroperitoneal tumor, when the renal artery was injured. Renal arteriography after the surgery demonstrated a segmental infarction of the right kidney. A close relationship between activation of the renin-angiotensin system and the development of severe hypertension was observed. Satisfactory control of blood pressure concomitant with reduction of plasma renin activity was achieved by a combination of an angiotensin-converting anzyme inhibitor, beta-blocking agent, and calcium-entry blocker. The mechanism of activation of the renin-angiotensin system in renal infarction is discussed.
The authors report a case with idiopathic orthostatic hypotension in which the patient prevents his blood pressure from falling to a symptomatic level by leg-crossing in a sitting position. Including 4 other patients with orthostatic hypotension and 5 normal subjects, their study found that the changes in blood pressure with leg-crossing inversely correlated with those induced by assuming seated posture from a supine position. Leg-crossing may, therefore, be one of the useful nonpharmacologic measures for maintaining blood pressure in a sitting position in patients with orthostatic hypotension.
To clarify the effect of dietary sodium restriction on the mechanism regulating sodium and water in the development of hypertension, we determined the number of the alpha-adrenoceptors in renal basolateral membrane in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The rats had been fed a low-sodium (0.5%) or normal-sodium (0.4%) diet from 3 weeks of age. The experiments were performed at 6, 8 and 20 weeks of age in both rat groups. Renal basolateral membranes were prepared using Percoll and radioligand binding studies were performed using 3H-prazosin and 3H-rauwolscine. Systolic blood pressure in SHR was already elevated at 6 weeks of age compared with that in WKY rats and rose to hypertensive levels at 8 weeks of age. The sodium balance in WKY rats on both diets decreased at 8 weeks of age, but that of SHR decreased at 20 weeks of age. The maximum number (Bmax) for the alpha 1-adrenoceptor did not differ in any groups of the WKY rats or SHR. Bmax for the alpha 2-adrenoceptors increased at 8 weeks of age in the low-sodium SHR compared with normal-sodium SHR, but did not increase in WKY rats. The data show that the increases in blood pressure in the SHR occur prior to significant increases in the alpha 2-adrenoceptor density of renal basolateral membrane, and that the modulation of alpha 2-adrenoceptor density in SHR differs from that in WKY rats under sodium restriction. The results suggest that renal alpha 2-adrenoceptors in SHR could relate the regulatory mechanism to sodium reabsorption under sodium restriction rather than to the primary cause of the development of hypertension in SHR. There may be the possibility of an abnormality in renal alpha 2-adrenoceptor mechanism in SHR.
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Carvedilol, a novel beta-blocker with a vasodilating action, was given either alone (monotherapy) or with diuretics (combination therapy) to 42 patients with renal hypertension. The hypotensive effect, safety, and optimal dose were investigated. In all, 23 untreated patients (16 men and 7 women; average age, 56.4 +/- 2.5 years) made up the monotherapy group and 19 diuretic-treated patients (11 men and 8 women; average age, 56.4 +/- 2.5 years) comprised the combined therapy group. All subjects had an initial blood pressure (BP) of greater than 160/95 mmHg and were started on 5 mg/day oral carvedilol. The dose was gradually increased to a maximum of 20 mg/day, or until either the BP was reduced to less than 149/89 mmHg or the reduction in mean BP was greater than 13 mmHg compared with baseline levels. The total study period was 8 weeks. With monotherapy, the BP and heart rate decreased significantly from 167/102 to 150/94 mmHg and from 81 to 74 beats/min, respectively. With combined therapy, the BP and heart rate fell significantly from 176/103 to 142/85 mmHg and from 81 to 70 beats/min, respectively. Responders were defined as subjects with a BP of less than or equal to 149/89 mmHg or those showing a fall of greater than or equal to 13 mmHg in mean BP. Responders accounted for 52.2% of the monotherapy group and 73.6% of the combination therapy group. Orthostatic hypotension was not seen in either group. Serum creatinine and blood urea nitrogen (BUN) levels were not altered by administration of carvedilol. Dizziness was noted by 1 of the 23 subjects in the monotherapy group.(ABSTRACT TRUNCATED AT 250 WORDS)
Under standardized conditions, we determined circadian urinary excretion of sodium (Na) and free dopamine (DA), norepinephrine (NE) and epinephrine (E) in 20 normotensive, 20 borderline hypertensive and 10 mild hypertensive middle-aged men. The 24-hour excretions of water, Na, DA, NE and E were comparable between the normotensives and the hypertensives. In the total study population, these parameters showed significant time-related changes: high excretion during the daytime and low excretion in the night. The circadian variations of urinary DA, NE and E were similar among the 3 groups. The circadian curve of urinary DA was similar to those of Na and water excretion. In the total study population, 24-hour water and Na excretion correlated positively with urinary DA, but not with NE or E. These results suggest that endogenous DA may play a role in the circadian variation of water and sodium metabolism. The circadian excretion of urinary catecholamines may not be altered in middle-aged subjects with borderline or mild hypertension.
Baroreflex function and plasma angiotensin II (Ang II) were examined in five elderly and five young or middle-aged essential hypertensive patients before and after enalapril treatment. Baroreflex sensitivity (BS) during blood pressure (BP) elevation by phenylephrine (PE) but not during BP reduction by sodium nitroprusside (SNP) was significantly attenuated in the elderly compared with the younger group, while plasma Ang II concentration was not different between the two groups. Enalapril treatment reduced BP without significant changes in heart rate and plasma norepinephrine in both groups, suggesting a leftward shift of barofunction curve. It also increased the BS in some cases in each group. However, plasma Ang II was not significantly reduced during enalapril treatment. The changes in BS did not correlate with changes in plasma Ang II. These results suggest that BS may be attenuated with increasing age independent of plasma Ang II and that ACE inhibitor influences the set point of the barofunction curve and BS by different mechanisms.
We performed exercise thallium-201 myocardial scintigraphy in 32 patients with angina pectoris to study the incidence of perfusion defects, who had no significant organic stenosis on coronary angiography. None of them had myocardial infarction or cardiomyopathy. Thallium-201 myocardial scintigraphy and 12-lead ECG recording were performed during supine bicycle ergometer exercise. Perfusion defects in thallium-201 scintigrams in SPECT images were assessed during visual analysis by two observers. In the coronary angiograms obtained during intravenous infusion of nitroglycerin, the luminal diameter of 75% stenosis or less in the AHA classification was regarded as an insignificant organic stenosis. Myocardial perfusion defects in the thallium-201 scintigrams were detected in eight (25%) of the 32 patients. Six of these eight patients had variant angina documented during spontaneous attacks with ST elevations in standard 12-lead ECGs. Perfusion defects were demonstrated at the inferior or inferoposterior regions in six patients, one of whom had concomitant anteroseptal defect. The defects were not always accompanied by chest pain. All but one patient demonstrating inferior or inferoposterior defects showed ST depression in leads II, III and aVF on their ECGs, corresponding to inferior wall ischemia. The exception was a case with right bundle branch block. Thus, 25% of the patients with angina pectoris, who had no evidence of significant organic stenosis on their coronary angiograms, exhibited exercise-induced perfusion defects in their thallium-201 scintigrams. Coronary spasms might have caused myocardial ischemia in these patients.
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Hypertensives screened among a work-site male population were treated either with or without antihypertensive drugs according to WHO stage of hypertension, and followed up by medical teams at the work site. The outcome during 8 years of follow-up was compared between two hypertension cohorts; one (cohort 1) instituted in 1970 included 1,092 hypertensives from 11,860 employees, while the other (cohort 2) made in 1975 contained 1,190 from 10,789 persons. Age-adjusted mortality or morbidity rate from cardiovascular diseases (CVD) was lower in cohort 2 than in cohort 1. Multiple regression analysis was used to adjust inter-cohort differences in factors to influence the prognosis, showed that CVD occurred less frequently in cohort 2 than in cohort 1. The results suggest that this system of controlling blood pressure is useful in preventing CVD in a large population.
We compared the levels of fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1) in non-insulin-dependent diabetics with hypertension who were treated with monotherapy of diuretics or other antihypertensive drugs (AHD) and in those who were not given any AHD. Total 162 patients were divided into the four groups; the control group without AHD (n = 45), the diuretics group (n = 42), the beta-blocker group (n = 30) and the Ca-antagonist group (n = 45). FPG and HbA1 levels were 153 +/- 44 mg/dl and 10.0 +/- 2.3% for the control group, 145 +/- 55 mg/dl and 9.8 +/- 2.2% for the diuretics, 165 +/- 63 mg/dl and 10.2 +/- 2.1% for the beta-blocker and 158 +/- 42 mg/dl and 10.4 +/- 2.0% for the Ca-antagonist, respectively. There were no significant differences in the levels of FPG and HbA1 among the four groups. Multivariate analysis also revealed no difference in glycemic control even when anti-diabetic treatment (diet alone, oral hypoglycemic agents or insulin), body mass index, serum potassium, systolic and diastolic blood pressures and age were taken into account. Blood pressure levels did not differ among the groups except control and they were well controlled at the low doses of AHD. Our results suggest that the choice of low dose diuretics for the treatment of hypertension in non-insulin-dependent diabetics might not be necessarily excluded by the only reason of the possible deleterious influence on glycemic control.
Plasma glucose levels in 50 g oral glucose tolerance test (OGTT) were compared between uncomplicated hypertensives (n = 507, mean age = 48 +/- 0.3 years) and normotensives (n = 378, mean age = 46 +/- 0.3 years). The subjects were selected in a systematic way from 10,120 male employees in a work-site population in Japan. None of hypertensives took any antihypertensive drugs. Plasma glucose levels at each time point of OGTT were significantly higher in the hypertensives than in the normotensives when the differences in age, obesity, and other factors that might influence glucose metabolism were adjusted, using multiple linear regression analysis. Similarly, multiple regression analysis for subjects including both normotensives and hypertensives revealed a significant relationship between plasma glucose levels and blood pressure, which was independent of age and body mass index. These findings indicate a more direct association between hypertension and hyperglycemia, which is not mediated via aging or obesity.
Carvedilol, a new beta-blocker with vasodilating activity, was given orally to 9 hypertensive inpatients with impaired renal function in a dosage regimen of 5 to 20mg once daily to evaluate its clinical efficacy and safety. Treatment with carvedilol produced a significant decrease in blood pressure from 172/101 to 150/87mm Hg (p less than 0.01), but it did not cause orthostatic hypotension. Heart rate was decreased from 74.3 to 72.8 beats/min, but the decrease was not statistically significant. Serum creatinine and BUN levels were unchanged and other laboratory parameters were within normal limits. There were no side effects in any of the patients during the trial. These results suggest that carvedilol is a useful and safe drug for the treatment of renal hypertension.
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