Terunao Ashida

Acute depressor effect of alcohol in patients with essential hypertension.

To investigate the time course of the effects of alcohol on blood pressure, we studied the response of ambulatory blood pressure, neurohumoral variables, and hemodynamics to a single moderate dose of alcohol in hypertensive patients. Sixteen Japanese men (22-70 years old) with essential hypertension who were habitual drinkers were examined under standardized conditions. On the alcohol intake day, they ingested 1 ml/kg ethanol (vodka) at dinner, and on the control day they consumed a nonalcoholic beverage. The order of the two periods was randomized. Mean ambulatory blood pressure was lower in the alcohol intake period than in the control period (125 +/- 3/74 +/- 2 versus 132 +/- 4/78 +/- 2 mm Hg, p less than 0.05), and the significant depressor effect of alcohol lasted for up to 8 hours after drinking. Blood pressure on the next day did not differ with or without alcohol intake. The acute hypotensive effect of alcohol was associated with an increase in heart rate and cardiac output and with a decrease in systemic vascular resistance as determined by echocardiography. Plasma catecholamine levels and renin activity rose significantly at 2 hours after dinner, whereas vasopressin and potassium levels fell on the alcohol day. Blood glucose and serum insulin levels were comparable between the two periods. Three patients with marked alcohol-induced flush had greater hypotensive and tachycardiac responses than those who did not show an alcohol-induced flush. The change in mean blood pressure induced by alcohol was negatively correlated with age, the baseline blood pressure, and the change in plasma norepinephrine. These results indicate that the major effect of acute alcohol intake is to lower blood pressure through systemic vasodilatation in hypertensive subjects. Ambulatory blood pressure monitoring may be useful for assessing blood pressure in habitual drinkers.

Biphasic effects of repeated alcohol intake on 24-hour blood pressure in hypertensive patients.

BACKGROUND The association between alcohol and blood pressure (BP) may be related to the temporal sequencing of alcohol use and BP measurement. We investigated the effects of single and repeated intakes of alcohol on 24-hour BP. METHODS AND RESULTS Fourteen male habitual drinkers with essential hypertension were placed sequentially on a 4-day control phase: a nonalcoholic drink with the same calories as alcohol was given at dinner (5 PM to 6 PM) and a 7-day drinking phase: alcohol (ethanol, 1 mL/kg) was given at dinner under standardized conditions. Ambulatory BP measurements were performed on day 3 of the control phase and on days 1 and 7 of the alcohol phase. The average 24-hour systolic and diastolic BPs on day 1 were significantly lower than those in the control phase and on day 7. Between 6 PM and midnight, both systolic and diastolic BPs on days 1 and 7 (121 +/- 2/73 +/- 1 and 126 +/- 4/75 +/- 2 mm Hg, respectively) were significantly lower than those in the control phase (139 +/- 4/83 +/- 2 mm Hg). Between midnight and 8 AM (6 to 14 hours after the last drink), both systolic and diastolic BPs on day 7 (138 +/- 4/83 +/- 2 mm Hg) were significantly higher than those in the control phase (131 +/- 4/79 +/- 2 mm Hg) and day 1 (129 +/- 3/77 +/- 1 mm Hg). Between 8 AM and 3 PM, BPs showed no difference among the three phases. CONCLUSIONS A single intake of alcohol has a depressor effect on BP that lasts for several hours after drinking, while repeated intakes for 7 days have both depressor and pressor effects according to the differences in time intervals after the last drink. This study suggests that the chronic effects of alcohol on BP might be overestimated when based on casual BP measurements alone.

Measurement of plasma brain natriuretic peptide level as a guide for cardiac overload.

OBJECTIVES We examined whether measurement of the plasma BNP concentrations might be useful for the early diagnosis of the existence and severity of disease in patients with heart disease in daily clinical practice. METHODS AND RESULTS The plasma BNP and ANP concentrations in 415 patients with heart disease and hypertension and 65 control subjects were measured. Patients with heart disease had higher plasma BNP and ANP concentrations than did those with hypertension or control subjects. Among the etiology of cardiac diseases, specifically dilated cardiomyopathy and hypertrophic cardiomyopathy, was associated with the highest plasma BNP concentrations, whereas dilated cardiomyopathy was associated with the highest plasma ANP concentrations. Plasma BNP concentrations showed an increase as the severity of the heart disease, as graded according to the NYHA classification of cardiac function, increased. In both patients with heart disease and hypertension, the plasma BNP values were higher in those who had abnormalities in their echocardiogram and electrocardiogram as compared to those without any abnormalities. The plasma BNP levels also showed a significant correlation with left ventricular wall thickness and left ventricular mass. On the other hand, the plasma ANP levels showed significant correlations with left ventricular dimension. Receiver operative characteristic analysis revealed that plasma BNP levels showed substantially high sensitivity and specificity to detect the existence of heart diseases. CONCLUSION Measurements of the plasma BNP concentrations is useful to detect the existence of the diseases, and abnormalities of left ventricular function and hypertrophy in patients with heart disease in daily clinical practice.

Renal function curve in patients with secondary forms of hypertension.

The causative mechanisms of hypertension were investigated by studying the renal function (pressure-natriuresis) curve in patients with primary aldosteronism (n = 6) and renovascular hypertension (n = 6). Before and after radical operation (removal of adenoma in primary aldosteronism and percutaneous transluminal angioplasty in renovascular hypertension), dietary NaCl intake was altered from 10 to 13 g/day in Week 1 to 1 to 3 g/day in Week 2. Mean arterial pressure (MAP) and urinary sodium excretion were measured on the last 3 days of each week. By restricting sodium intake before operation, MAP was reduced from 122 +/- 7 to 113 +/- 7 mm Hg (p less than 0.025) in primary aldosteronism but not in renovascular hypertension (130 +/- 6 to 128 +/- 5 mm Hg). The renal function curve was drawn by plotting urinary sodium excretion on the ordinate and MAP on the abscissa before and after operation. The slope of the curve was analyzed between the plotted points, and each curve was extrapolated to zero sodium excretion as an estimate of the degree of shift of the curve along the MAP axis. Before, as compared with after operation, the extrapolated x-intercept of the curve was shifted rightward in both primary aldosteronism (111 +/- 7 vs 87 +/- 4 mm Hg; p less than 0.025) and renovascular hypertension (128 +/- 5 vs 95 +/- 2 mm Hg; p less than 0.025) and the slope was depressed in primary aldosteronism (16 +/- 1 vs 40 +/- 17 [mEq/day]/mm Hg; p less than 0.025) but not in renovascular hypertension (130 +/- 75 vs 40 +/- 13 [mEq/day]/mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

SODIUM AND NORADRENALINE IN CEREBROSPINAL FLUID AND BLOOD IN SALT‐SENSITIVE AND NON‐SALT‐SENSITIVE ESSENTIAL HYPERTENSION

1. The effects of dietary sodium on blood pressure and levels of sodium, other electrolytes and noradrenaline (NA) in the cerebrospinal fluid (CSF) and blood of 15 patients with essential hypertension were studied. The CSF and blood sampling was carried out after 7 days of a high salt intake (16–18 g/day) and after 7 days of a low salt intake (1–3 g/day).

Acute effects of alcohol ingestion on blood pressure and erythrocyte sodium concentration

Objective To examine the acute effects of alcohol on blood pressure and erythrocyte cation concentrations in patients with essential hypertension. Design An alcoholic drink or an isocaloric control drink was given during supper in random order on different days, and blood pressure and erythrocyte cation concentrations were measured before and 2 h after the meal. Methods The subjects were 21 men with essential hypertension who habitually drank alcohol. Blood pressure was measured with a semi-automated sphygmomanometer, and erythrocyte cation concentrations were measured by flame photometry after haemolysis with distilled water. Results Blood pressure decreased after both drinks, but the decrease was significantly larger after the alcoholic drink than after the control drink. There was a significant difference between the changes in erythrocyte sodium caused by the alcoholic and the control drink. Furthermore, there were significant positive correlations between the fall in blood pressures and the decrease in erythrocyte sodium concentration. Conclusion The predominant acute effect of alcohol ingestion in patients with hypertension is blood pressure reduction, and it may be associated with a decrease in intracellular sodium.

Increased sodium-calcium exchange in arterial smooth muscle of spontaneously hypertensive rats.

We compared sodium-calcium (Na-Ca) exchange in vascular smooth muscle between spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Aortic rings of 11 SHR and 11 WKY rats aged 11–12 weeks were superfused with physiological saline, and isometric tension was measured. Systolic blood pressure was higher in SHR (174±12 mm Hg) than in WKY rats (132±4 mm Hg): 1) In the presence of 10 μM phentolamine, 10 μM verapamil, and 5 mM caffeine, reduction of ionized extracellular sodium concentration ([Na+]0) from normal (139.2 mM) to 1.2 mM (replaced by N-methyl-D-glucamine) caused an external Ca2+-dependent increase in tonic tension (calcium entry by Na-Ca exchange). The rate of increase was higher in SHR (35.4±3.9 mg/min) than in WKY rats (17.9+1.3 mg/min) (p < 0.01). 2) In the presence of phentolamine, verapamil, and caffeine, relaxation from low-Na+ contraction was promoted by external calcium removal. The rate of relaxation was directly related to [Na+]0. The rates of relaxation at normal (139.2 mM) [Na+]0 were higher in SHR than in WKY rats (p < 0.05). The rates of relaxation at 1.2 mM [Na+]0 (calcium extrusion by adenosine triphosphate-driven calcium pump) were not different between SHR (11.6±2.8 mg/min) and WKY rats (8.9±2.5 mg/min). The increase in the rates of relaxation from 1.2 mM to normal (139.2 mM) [Na+]0 (calcium extrusion by Na-Ca exchange) was greater in SHR (34.9±6.6 mg/min) than in WKY rats (17.1±4.5 mg/min) (p < 0.05). These observations suggest that Na-Ca exchange in vascular smooth muscle is increased in SHR and might be involved in the mechanisms for hypertension in SHR.

Effects of Short-Term Hypocaloric Diet on Sympatho-Vagal Interaction Assessed by Spectral Analysis of Heart Rate and Blood Pressure Variability during Stress Tests in Obese Hypertensive Patients

We examined the effects of a short-term low-calorie diet on the activity of the autonomic nervous system during stress tests in obese patients with hypertension by analysis of heart rate and blood pressure variability. Eighteen obese inpatients with essential hypertension were given a regular-calorie diet (1,600 kcal, NaCl 7 g) for 4 days, and then a low-calorie diet (1,100 kcal, NaCl 7 g) for 11 days. During both the regular-calorie diet and low-calorie diet, power spectral analysis of heart rate and blood pressure variability at rest and during mental arithmetic test, deep breathing test, isometric handgrip test or cold pressor test was performed. Body weight and 24-h ambulatory blood pressure were significantly lower during the low-calorie diet than during the regular-calorie diet. Systolic and diastolic blood pressure significantly increased over the handgrip test and cold pressor test during both diets. The low frequency component (LF) of systolic blood pressure, a marker of sympathetic activity to the vasculature, during the deep breathing test and cold pressor test were significantly lower on the low-calorie diet than the regular-calorie diet. The blood leptin concentration was also significantly lower on the low-calorie diet than the regular-calorie diet. The decrease in body weight was positively correlated with the decrease in blood leptin concentration. The LF/high frequency component (HF) ratio of the RR interval at rest on the regular-calorie diet was negatively correlated with the decrease in blood leptin concentration. These results suggest that the autonomic nervous function assessed by analysis of heart rate and blood pressure variability during stress tests may be improved by weight loss due to a short-term low-calorie diet in obese patients with hypertension.

Effect of a Calcium-Entry Blocker, Nicardipine, on Intrarenal Hemodynamics in Essential Hypertension

The effects of a calcium-entry blocker, nicardipine, on intrarenal hemodynamics were studied in essential hypertension. A 4-week study was performed in eight patients with essential hypertension who were given a regular sodium diet in the first and third weeks, and a sodium-restricted diet in the second and fourth weeks. Nicardipine, 60 mg/d, was administered in the third and fourth weeks. The urinary sodium excretion rate (UNaV) was plotted on the y-axis against the mean arterial pressure (MAP) on the x-axis before and after the administration of nicardipine. Assuming the difference between MAP and the x-intercept of this renal function curve represents the effective filtration pressure across the glomerular capillaries, the intrarenal hemodynamics such as afferent arteriolar resistance (RA) and efferent arteriolar resistances (RE), glomerular pressure (PG), and gross filtration coefficient (KFG) were calculated. Although the MAP on regular salt diet was lowered from 125 +/- 3 to 109 +/- 2 mm Hg by nicardipine, neither the renal blood flow rate (RBF) (670 +/- 40 mL/min) nor the glomerular filtration rate (GFR) (79 +/- 2 mL/min) was altered. The RA was estimated to be reduced from 9,300 +/- 900 to 7,400 +/- 700 dyne.s.cm-5 (P less than 0.01), while no changes were noted in RE (4,900 +/- 400 dyne.s.cm-5), PG (50 +/- 1 mm Hg), or KFG (0.180 +/- 0.041 [mL/s]/mm Hg). Essential hypertension has been characterized by a prominent increase in RA, resulting in maintenance of normal PG. This Ca-entry blocker worked to normalize intrarenal hemodynamics in essential hypertension by dilating afferent arterioles alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dietary sodium on platelet alpha 2-adrenergic receptors in essential hypertension.

To study the aggregation, adhesion, and specific binding of an alpha 2-antagonist, [3H]rauwolscine, to the platelet membrane fractions, platelets were obtained from 30 patients with essential hypertension and nine normotensive subjects fed a high sodium diet (NaCl, 16-18 g/day) for 7 days and thereafter a low sodium diet (NaCl, 1-3 g/day) for 7 days. The patients with essential hypertension were classified as either salt responders (all those who had greater than 7% decrease in mean arterial pressure from the high to low sodium period) or salt nonresponders (all others). In salt responders, the number of alpha 2-adrenergic receptors on platelet membrane fraction was increased from 523.4 +/- 55.4 fmol/mg of protein in the high sodium period to 669.4 +/- 84.0 fmol/mg of protein in the low sodium period (p less than 0.01), whereas it did not change in salt nonresponders. In contrast, the epinephrine-induced platelet aggregation through alpha 2-adrenergic receptors was decreased in nonresponders, from 47.3 +/- 7.4% in the high sodium period to 24.5 +/- 9.3% in the low sodium period (p less than 0.05), while it did not change in responders. No significant change in the number of alpha 2-adrenergic receptors or epinephrine-induced platelet aggregation was observed in the normotensive subjects.