Kaoru Yoshida

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.

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.

The cardiovascular effect of intracerebroventricular endothelin in rats

To investigate the cardiovascular action of endothelin within the central nervous system, we studied the effect of intracerebroventricular endothelin in conscious Wistar rats. The endothelin increased blood pressure and the heart rate in a dose-related way. The increase in mean blood pressure produced by 100 ng/kg of endothelin (45 +/- 6 mmHg, mean +/- s.e.m., n = 10) was much greater than that produced by the same amount of intravenous endothelin (4 +/- 1 mmHg, n = 7). Pretreatment with intravenous hexamethonium significantly attenuated the rise in blood pressure elicited by intracerebroventricular endothelin. Combined administration of hexamethonium and a vasopressin antagonist abolished the pressor response. These results indicate that centrally administered endothelin raises blood pressure through activation of the sympathetic nervous system and vasopressin. It is suggested that endothelin may play a role in the central regulation of cardiovascular function.

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)

Measurement of left atrial systolic time intervals in hypertensive patients using Doppler echocardiography: Relation to fourth heart sound and left ventricular wall thickness

The concept of left atrial systolic time intervals and Doppler echocardiography were used in a quantitative assessment of left atrial function in relation to the presence or absence of a fourth heart sound and to left ventricular hypertrophy in 47 patients with hypertension. Left atrial systolic time interval indexes included atrial pre-ejection period (the time between the onset of an electrocardiographic P wave and the onset of left ventricular inflow during atrial systole [A wave]), corrected atrial pre-ejection period (the atrial pre-ejection period divided by the duration of the P wave), and atrial ejection time (the time between the onset and cessation of the A wave). Twenty-one patients with a fourth heart sound on the phonocardiogram had a shorter atrial pre-ejection period (81 +/- 10 versus 89 +/- 14 ms p less than 0.05) and a corrected atrial pre-ejection period (66 +/- 17 versus 83 +/- 18 ms, p less than 0.01), as well as a longer atrial ejection time (147 +/- 15 versus 126 +/- 13 ms, p less than 0.001) than did 26 patients without a fourth heart sound. The ratio of atrial pre-ejection period to atrial ejection time and that of corrected atrial pre-ejection period to atrial ejection time was smaller in patients with than in patients without a fourth heart sound (0.56 +/- 0.08 versus 0.71 +/- 0.11, p less than 0.001; 0.46 +/- 0.16 ms-1 versus 0.67 +/- 0.17 ms-1, p less than 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of nifedipine SR and enalapril on office, home and ambulatory blood pressure in “white-coat” systemic hypertension☆

Abstract Among patients who were found to have hypertension by office or clinic blood pressure (BP) measurement, some appear to be normotensive when studied for full 24-hour periods by ambulatory BP monitoring, indicating so-called “office” or “white-coat” hypertension. Within groups of hypertensive patients with similar office BPs, those with higher than predicted ambulatory BP have greater prevalence of target-organ damage 1,2 and a significantly greater 10-year incidence of fatal and unfatal events than those with lower than predicted ambulatory BP. 3 Moreover, there is some indication that reducing BP too much may exert a deleterious rather than a beneficial effect on coronary events. 4 In the present study, we examined and compared the effects of the long-acting calcium antagonist nifedipine slow-release tablet (nifedipine SR) with the effects of the long-acting angiotensin converting enzyme inhibitor enalapril on office, home and ambulatory BP measurements. We studied hypertensive patients with relatively higher and relatively lower ambulatory BPs.

A Sensitive Method for Precise Measurement of Endogenous Angiotensins I, II&III in Human Plasma

We measured endogenous angiotensins (ANGs) I, II&III using a system of extraction by Sep-Pak column followed by high performance liquid chromatography (HPLC) combined with radioimmunoassay (RIA). An excellent separation of ANGs was obtained by HPLC. The recovery of ANGs I, II&III was 80-84%, when these authentic peptides were added to 6 ml of plasma. The coefficient of variation of the ANGs was 0.04-0.09 for intra-assay and 0.08-0.13 for inter-assay, thereby indicating a good reproducibility. Plasma ANGs I, II&III measured by this method in 5 normal volunteers were 51,4.5 and 1.2 pg/ml. In the presence of captopril, ANGs II&III decreased by 84% and 77%, respectively, while ANG I increased 5.1 times. This method is therefore useful to assess the precise levels of plasma ANGs.

Immunoreactive endothelin-1 contents in brain regions from spontaneously hypertensive rats.

To investigate the possible role of brain endothelin-1 (ET-1) in hypertension of spontaneously hypertensive rats (SHRs), we measured immunoreactive (ir) ET-1 contents in brain regions as well as plasma ir-ET-1 levels in SHRs aged 4-5 and 12-14 weeks and age-matched Wistar-Kyoto rats (WKY) with a radioimmunoassay for ET-1. Systolic blood pressures of SHR aged 4-5 and 12-14 weeks were significantly higher than those of corresponding WKY. Significant amounts of ir-ET-1 were detectable throughout the discrete brain regions analyzed in both strains; higher ir-ET-1 contents in structures such as thalamus, hypothalamus, midbrain, pons, medulla, and cerebellum, with the lowest in cerebral cortex, were observed. A reverse-phase high-performance liquid chromatography of the brain extracts revealed the presence of both a major component identical to the elution position of synthetic ET-1 and a minor component possibly corresponding to its oxidized form. When compared, ir-ET-1 contents in all brain regions analyzed were lower in SHRs than in WKY rats. This strain-related change of ir-ET-1 contents was significant in the medulla at 4-5 weeks of age, and in all brain regions except hypothalamus at 12-14 weeks of age. Plasma ir-ET-1 levels, in contrast, were comparable between SHRs and WKY rats. These results suggest that brain ET-1 may be involved in the development and the maintenance of hypertension in SHRs.